CN109223744A - 鱼腥草素钠在制备用于防治糖尿病心脏病产品中的应用 - Google Patents
鱼腥草素钠在制备用于防治糖尿病心脏病产品中的应用 Download PDFInfo
- Publication number
- CN109223744A CN109223744A CN201811325039.5A CN201811325039A CN109223744A CN 109223744 A CN109223744 A CN 109223744A CN 201811325039 A CN201811325039 A CN 201811325039A CN 109223744 A CN109223744 A CN 109223744A
- Authority
- CN
- China
- Prior art keywords
- product
- sodium houttuyfonate
- preparation
- diabetes
- application
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 206010012601 diabetes mellitus Diseases 0.000 title claims abstract description 56
- HPPWMWCITPGPKK-UHFFFAOYSA-M sodium;1-hydroxy-3-oxododecane-1-sulfonate Chemical compound [Na+].CCCCCCCCCC(=O)CC(O)S([O-])(=O)=O HPPWMWCITPGPKK-UHFFFAOYSA-M 0.000 title claims abstract description 45
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 210000004369 blood Anatomy 0.000 claims abstract description 31
- 239000008280 blood Substances 0.000 claims abstract description 31
- 230000037149 energy metabolism Effects 0.000 claims abstract description 16
- 150000002632 lipids Chemical class 0.000 claims abstract description 13
- 208000031229 Cardiomyopathies Diseases 0.000 claims abstract description 11
- 208000021908 Myocardial disease Diseases 0.000 claims abstract description 11
- 239000008103 glucose Substances 0.000 claims description 16
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 13
- 229940079593 drug Drugs 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 230000036541 health Effects 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 3
- 208000013875 Heart injury Diseases 0.000 abstract description 8
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 abstract description 6
- 229930186217 Glycolipid Natural products 0.000 abstract description 6
- 238000002474 experimental method Methods 0.000 abstract description 6
- 230000004060 metabolic process Effects 0.000 abstract description 6
- 230000005856 abnormality Effects 0.000 abstract description 5
- 230000033228 biological regulation Effects 0.000 abstract description 5
- 230000009467 reduction Effects 0.000 abstract description 4
- 230000003293 cardioprotective effect Effects 0.000 abstract description 2
- 230000012666 negative regulation of transcription by glucose Effects 0.000 abstract description 2
- 230000002265 prevention Effects 0.000 abstract description 2
- 230000003449 preventive effect Effects 0.000 abstract description 2
- 230000001225 therapeutic effect Effects 0.000 abstract description 2
- 241000700159 Rattus Species 0.000 description 38
- 210000002966 serum Anatomy 0.000 description 22
- 210000001519 tissue Anatomy 0.000 description 21
- 230000000747 cardiac effect Effects 0.000 description 19
- 239000000047 product Substances 0.000 description 19
- 230000000694 effects Effects 0.000 description 15
- 230000003387 muscular Effects 0.000 description 15
- 210000004165 myocardium Anatomy 0.000 description 15
- ZKHQWZAMYRWXGA-KQYNXXCUSA-N Adenosine triphosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-N 0.000 description 14
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 13
- DRBBFCLWYRJSJZ-UHFFFAOYSA-N N-phosphocreatine Chemical compound OC(=O)CN(C)C(=N)NP(O)(O)=O DRBBFCLWYRJSJZ-UHFFFAOYSA-N 0.000 description 10
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 10
- 238000000034 method Methods 0.000 description 10
- UDMBCSSLTHHNCD-KQYNXXCUSA-N adenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O UDMBCSSLTHHNCD-KQYNXXCUSA-N 0.000 description 9
- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 8
- XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- 229960000830 captopril Drugs 0.000 description 8
- 108020004999 messenger RNA Proteins 0.000 description 8
- 230000002107 myocardial effect Effects 0.000 description 8
- 108700038399 PGC-1 Proteins 0.000 description 7
- 102000017946 PGC-1 Human genes 0.000 description 7
- 229950006790 adenosine phosphate Drugs 0.000 description 7
- 238000005259 measurement Methods 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- -1 phosphate compound Chemical class 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 108091006112 ATPases Proteins 0.000 description 5
- 102000057290 Adenosine Triphosphatases Human genes 0.000 description 5
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 5
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 5
- 101800000407 Brain natriuretic peptide 32 Proteins 0.000 description 5
- 102400000667 Brain natriuretic peptide 32 Human genes 0.000 description 5
- 101800002247 Brain natriuretic peptide 45 Proteins 0.000 description 5
- 229950007002 phosphocreatine Drugs 0.000 description 5
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 5
- 102100036009 5'-AMP-activated protein kinase catalytic subunit alpha-2 Human genes 0.000 description 4
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 4
- 108010082126 Alanine transaminase Proteins 0.000 description 4
- 101000783681 Homo sapiens 5'-AMP-activated protein kinase catalytic subunit alpha-2 Proteins 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- IOMXCGDXEUDZAK-UHFFFAOYSA-N chembl1511179 Chemical compound OC1=CC=C2C=CC=CC2=C1N=NC1=NC=CS1 IOMXCGDXEUDZAK-UHFFFAOYSA-N 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 210000005003 heart tissue Anatomy 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- 235000020995 raw meat Nutrition 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 229960001052 streptozocin Drugs 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 235000000346 sugar Nutrition 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 241000251468 Actinopterygii Species 0.000 description 3
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 3
- 244000025254 Cannabis sativa Species 0.000 description 3
- UDMBCSSLTHHNCD-UHFFFAOYSA-N Coenzym Q(11) Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(O)=O)C(O)C1O UDMBCSSLTHHNCD-UHFFFAOYSA-N 0.000 description 3
- 108010023302 HDL Cholesterol Proteins 0.000 description 3
- 206010019280 Heart failures Diseases 0.000 description 3
- 240000000691 Houttuynia cordata Species 0.000 description 3
- 238000008214 LDL Cholesterol Methods 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 3
- 229960005305 adenosine Drugs 0.000 description 3
- 239000007853 buffer solution Substances 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 230000004064 dysfunction Effects 0.000 description 3
- 230000002526 effect on cardiovascular system Effects 0.000 description 3
- 230000004217 heart function Effects 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 230000016507 interphase Effects 0.000 description 3
- 230000002438 mitochondrial effect Effects 0.000 description 3
- 210000003205 muscle Anatomy 0.000 description 3
- 230000003680 myocardial damage Effects 0.000 description 3
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 208000032781 Diabetic cardiomyopathy Diseases 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 235000013717 Houttuynia Nutrition 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 241000758742 Saururaceae Species 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- LNQVTSROQXJCDD-UHFFFAOYSA-N adenosine monophosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(CO)C(OP(O)(O)=O)C1O LNQVTSROQXJCDD-UHFFFAOYSA-N 0.000 description 2
- 230000006793 arrhythmia Effects 0.000 description 2
- 206010003119 arrhythmia Diseases 0.000 description 2
- 210000004413 cardiac myocyte Anatomy 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 208000029078 coronary artery disease Diseases 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000010627 oxidative phosphorylation Effects 0.000 description 2
- 230000036542 oxidative stress Effects 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000004224 protection Effects 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000000718 qrs complex Methods 0.000 description 2
- 238000011552 rat model Methods 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
- 230000002861 ventricular Effects 0.000 description 2
- KIUMMUBSPKGMOY-UHFFFAOYSA-N 3,3'-Dithiobis(6-nitrobenzoic acid) Chemical compound C1=C([N+]([O-])=O)C(C(=O)O)=CC(SSC=2C=C(C(=CC=2)[N+]([O-])=O)C(O)=O)=C1 KIUMMUBSPKGMOY-UHFFFAOYSA-N 0.000 description 1
- XLYLQUQHYUOPIW-UHFFFAOYSA-N 3-oxo-Tetradecanal Chemical compound CCCCCCCCCCCC(=O)CC=O XLYLQUQHYUOPIW-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 241000758794 Asarum Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 240000008100 Brassica rapa Species 0.000 description 1
- 235000011292 Brassica rapa Nutrition 0.000 description 1
- 206010006458 Bronchitis chronic Diseases 0.000 description 1
- CHTUTNRSUGMGBL-UHFFFAOYSA-N C(CCCCCCCCC)(=O)CC=O.C(C)=O Chemical compound C(CCCCCCCCC)(=O)CC=O.C(C)=O CHTUTNRSUGMGBL-UHFFFAOYSA-N 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- 244000131522 Citrus pyriformis Species 0.000 description 1
- QBDCOUHKEVYWLO-UHFFFAOYSA-N Decanoylacetaldehyde Natural products CCCCCCCCCC(=O)CC=O QBDCOUHKEVYWLO-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 206010018429 Glucose tolerance impaired Diseases 0.000 description 1
- 206010018473 Glycosuria Diseases 0.000 description 1
- 108010010234 HDL Lipoproteins Proteins 0.000 description 1
- 102000015779 HDL Lipoproteins Human genes 0.000 description 1
- 241000606768 Haemophilus influenzae Species 0.000 description 1
- 235000013719 Houttuynia cordata Nutrition 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 240000003271 Leonurus japonicus Species 0.000 description 1
- 208000031662 Noncommunicable disease Diseases 0.000 description 1
- 244000131316 Panax pseudoginseng Species 0.000 description 1
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 1
- 235000003140 Panax quinquefolius Nutrition 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 208000001280 Prediabetic State Diseases 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N adenyl group Chemical class N1=CN=C2N=CNC2=C1N GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000002058 anti-hyperglycaemic effect Effects 0.000 description 1
- 230000002567 autonomic effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229940095731 candida albicans Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 230000005961 cardioprotection Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 208000007451 chronic bronchitis Diseases 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 230000008828 contractile function Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000035611 feeding Effects 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 235000021588 free fatty acids Nutrition 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 235000008434 ginseng Nutrition 0.000 description 1
- 230000002641 glycemic effect Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229940047650 haemophilus influenzae Drugs 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000009940 knitting Methods 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 230000006676 mitochondrial damage Effects 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 208000037891 myocardial injury Diseases 0.000 description 1
- HPNRHPKXQZSDFX-OAQDCNSJSA-N nesiritide Chemical compound C([C@H]1C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)CNC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CO)C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1N=CNC=1)C(O)=O)=O)[C@@H](C)CC)C1=CC=CC=C1 HPNRHPKXQZSDFX-OAQDCNSJSA-N 0.000 description 1
- 230000000474 nursing effect Effects 0.000 description 1
- 238000011017 operating method Methods 0.000 description 1
- 238000003305 oral gavage Methods 0.000 description 1
- 229940100688 oral solution Drugs 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000035778 pathophysiological process Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 201000009104 prediabetes syndrome Diseases 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000011506 response to oxidative stress Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 229940079827 sodium hydrogen sulfite Drugs 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229940098465 tincture Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 208000011479 upper respiratory tract disease Diseases 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Cardiology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Botany (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明公开了一种鱼腥草素钠在制备用于防治糖尿病心脏病产品中的应用。鱼腥草素钠可用于制备防治糖尿病心脏病、调控心肌能量代谢紊乱、改善糖脂代谢异常的产品。本发明经实验证实：(1)鱼腥草素钠对糖尿病心脏病有防治作用，有心脏保护效果；(2)可调控心肌能量代谢紊乱；(3)可降低糖尿病引起血脂升高，有一定的降低血糖作用。在制备用于防治糖尿病引起的心脏损伤、心肌能量代谢紊乱、糖脂代谢异常等的产品方面具有良好的临床应用前景。
Description
技术领域
本发明涉及一种鱼腥草素钠在制备用于防治糖尿病心脏病产品中的应用，属于医药技术领域。
背景技术
(一)糖尿病心脏病并发症及流行病学调查
糖尿病是当前威胁人类健康最重要的非传染性疾病之一，我国20岁以上人群中糖尿病患者约9.7％，糖尿病前期的比例达15.5％，而其中只有40％患者获得诊断(中华医学会糖尿病学分会.中国2型糖尿病防治指南(2013年版).中国医学前沿杂志(电子版)，2015，(03):26-89.)。糖尿病心脏病(diabetic cardiopathy)是糖尿病最主要的并发症，在糖尿病患者中患心脏并发症在75％左右(Ofstad AP.Myocardial dysfunction andcardiovascular disease in type 2 diabetes.Scand J Clin Lab Invest,2016,76(4):271-81.)，主要的表现包括糖尿病心肌病变、冠心病、糖尿病性心脏自主神经功能紊乱所致的心律失常、心功能不全等，是糖尿病患者生存质量的主要影响因素和致死的首要原因，患者心脑血管疾病的风险较非糖尿病人群增加2-4倍，平均寿命减少8年左右，因糖尿病心脏病而死亡的约占糖尿病患者死亡人数的60-70％(Luthra S,Leiva-Juárez MM,TaggartDP.Systematic review of therapies for stable coronary artery disease indiabetic patients.Ann Thorac Surg,2015,100(6):2383-97.)。
目前以补充胰岛素或纠正胰岛分泌等方式控制血糖水平等基础治疗为主，然而单纯血糖控制对于减少糖尿病患者心脑血管损伤及所致死亡风险的作用是有限的，临床上对已经发展成糖尿病心脏病的病人还没有有效的治疗方法，心脏损伤一旦发生很难逆转。
(二)糖尿病心脏病的心肌能量代谢紊乱与调控
心脏是高耗能的器官，心肌细胞内储存的高能磷酸化合物(如ATP)浓度极低，所需能量需心肌细胞不断通过复杂环节将血液中营养物质经氧化磷酸化产生ATP供应。通常在糖尿病确诊前，心血管病变已经发生，在高糖高脂和胰岛素缺乏或抵抗等因素诱导下，通过多种复杂机制最终造成微血管、心肌细胞结构功能改变，其中间过程的复杂机制中，心肌能量代谢紊乱为中心环节和始动因素(Fuentes-Antrás J,Picatoste B,Ramírez E,etal.Targeting metabolic disturbance in the diabetic heart.Cardiovasc Diabetol,2015,14:17.)，是心脏功能异常时病理生理过程的早期事件，能量底物转运利用的障碍，参与能量物质生成的葡萄糖进入细胞内的量减少，进而转为主要由脂肪酸β氧化供应能量，引起脂代谢有毒代谢产物如游离脂肪酸增多，导致心脏功能受损(Tillquist MN,MaddoxTM.Update on diabetic cardiomyopathy:inches forward,miles to go.Curr Diab Rep,2012,12(3):305-13.)；在氧化磷酸化环节，线粒体是主要的细胞器，糖尿病会引起心肌线粒体的损伤，导致心脏能量代谢的紊乱，引起收缩功能的受损。因此，心脏能量代谢的紊乱，贯穿糖尿病诱发心脏损伤的整个发展过程。
(三)鱼腥草素钠
本品为中药三白草科(Saururaceae)蕺菜属(Houttuynia cordata Thunb)植物鱼腥草的主要挥发性成分鱼腥草素(癸酰乙醛)和亚硫酸氢钠加成物，化学名癸酰乙醛合亚硫酸氢钠。目前临床上主要用于慢性支气管炎及其他上呼吸道感染性疾病等。药理作用主要为对细菌只有微弱的抗菌作用，对金黄色葡萄球菌、流感嗜血杆菌、白念珠菌等有一定抑制作用。关于鱼腥草素钠对糖尿病引起的心脏损伤作用、改善糖脂代谢和改善心肌能量代谢方面的研究并未有报道。也未见有关于鱼腥草素钠在该方面作用的发明专利。
发明内容
本发明目的是提供鱼腥草素钠的一种新用途，其新用途是指鱼腥草素钠用于防治糖尿病引起的心脏病并发症、调控心肌能量代谢紊乱、改善糖尿病引起的糖脂代谢异常以及其他原因引起的血脂升高的产品。本发明的技术方案具体介绍如下。
鱼腥草素钠在制备用于防治糖尿病心脏病产品中的应用。
鱼腥草素钠在制备防治糖尿病引起的血糖升高产品中的应用。
鱼腥草素钠在制备防治糖尿病引起的血脂升高及相关性疾病产品中的应用。
鱼腥草素钠在制备改善糖尿病引起的心肌能量代谢紊乱产品中的应用。
上述产品包括与鱼腥草素钠相同化学结构的物质，以及与鱼腥草素相同结构的物质。
上述的产品包括药物、制剂或保健品中的一种。
上述的产品中，还可以包括药学上或食品学上可接受的载体。
上述的产品的剂型可以是多种多样的，只要是能够使活性成分有效地到达体内的剂型都是可以的。比如可选自：片剂、胶囊剂、粉末、颗粒剂、糖浆、溶液、悬浮液、注射剂、酊剂、口服液、气雾剂、***剂、冲剂、丸剂、散剂等常见剂型或纳米制剂等缓释剂型。
本发明所述活性物质的有效施用剂量可随所用的给药模式和待治疗的疾病的严重程度而变化。在制备用于防治糖尿病引起的心脏损伤、心肌能量代谢紊乱、糖脂代谢异常等的产品方面具有良好的临床应用前景。
具体实施方式
下面结合具体实施例，进一步阐述本发明。应理解，这些实施例仅用于说明本发明而不用于限制本发明的范围。
本发明采用国内外学术界已广泛应用的糖尿病的造模方法，主要采用腹腔注射链脲佐菌素85mg/kg诱导产生血糖升高，进一步诱发心脏损伤和心脏功能不全的大鼠模型。模拟临床口服给药途径，采用灌胃方式将鱼腥草素钠给予模型动物进行干预。
以血糖水平评价糖尿病模型的是否成功；实验结束时测量大鼠血糖、血脂水平，测定心电图变化，检测心衰标志物(血清BNP、AST、ALT水平)，测量氧化应激反应相关指标、心肌线粒体离子通道相关酶的变化；测量心肌能量代谢相关高能磷酸化合物以及能量代谢信号通路相关基因的改变，从而评价药物作用效果。
实施例1：鱼腥草素钠对糖尿病大鼠心脏保护作用研究
实验材料
1.药品及制备链脲佐菌素(Streptozocin，批号：WXBC4439V)，德国Sigma-alorich公司产品；鱼腥草素钠(批号：06161204，含量大于标示量的93.0％，符合药典规定)，上海青平制药有限公司产品；卡托普利(批号：AAP7365)，中美上海施贵宝制药有限公司产品。鱼腥草素钠和卡托普利在使用前用蒸馏水溶解，链脲佐菌素使用前使用时溶解于0.1mol/L柠檬酸酸缓冲液中(10mg/mL)，避光，现用现配。
2.动物健康雄性大鼠(Sprague Dawley 200-220g)，清洁级，购买于上海斯莱克实验动物有限责任公司，动物生产许可证号:SCXK(沪)2012-0002。所有大鼠饲养在温度22-24℃，湿度40-45％和12小时交替的黑暗与光明的环境中，自由饮水和进食。实验动物的使用遵循美国国立卫生院颁布的实验动物护理和使用指南(NIH Publication No.85-23,1996)和上海中医药大学动物护理与使用委员会的规定。
实验方法
1.模型制备方法 大鼠随机分为正常对照组和造模组。禁食12小时后，造模组大鼠一次性腹腔注射1％的链脲佐菌素(溶解于PH值为4.5的柠檬酸钠缓冲液)溶液，剂量为85mg/kg，正常对照组大鼠注射等量柠檬酸钠缓冲液。注射STZ 3天后，使用罗氏血糖仪(德国)检测各组大鼠空腹血糖(FBG)。FBG≥16.7mmol/L的大鼠为糖尿病动物。
2.分组和给药方法 将糖尿病模型动物随机分为糖尿病组、卡托普利组(50mg/kg)，鱼腥草素钠小剂量组(50mg/kg)、鱼腥草素钠大剂量组(100mg/kg)，正常对照组和模型组大鼠灌胃给予蒸馏水，其余各组大鼠按剂量分别灌胃给药，给药体积为1mL/100g，每天一次，连续给药26天。
3.动物处理与样本采集方法 在实验结束时，大鼠禁食12小时后，称量体重(BM)，所有大鼠均腹腔注射乌拉坦麻醉(1g/kg)，记录心电图(ECG)。腹主动脉取血后，在1972g的速度下离心10分钟收集血清；分离心脏组织后称取左心室重量(LVM)，并计算左心重指数(LVMI＝LVM/BM)，心脏组织与血清储存于-80℃的冰箱中备用。
4.观察指标和检测方法
4.1空腹血糖值的测量：使用日立7080生化分析仪测定各组大鼠血清中FBG，根据测量结果对各组大鼠的空腹血糖水平进行评价。
4.2血脂水平测量：血清中甘油三酯(TG)和总胆固醇(TC)的含量使用日立7080生化分析仪来测定；血清低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)水平使用相应试剂盒在酶标仪上进行检测，操作遵循试剂盒说明书。
4.3血清MDA含量测定：采用试剂盒以酶标仪采用DTNB法检测血清中MDA含量。具体操作遵循试剂盒说明书。
4.4心脏损伤标志物的检测：使用日立7080生化分析仪对血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)进行检测。用酶联免疫吸附法测定血清中BNP含量，按试剂盒说明书进行操作。
4.5心电图的评估：大鼠心电图使用RM6240B型多通道生物信号***记录。统计心率、P-R、QRS波段、S-T和Q-T间期来评价各组大鼠心电图的改变。
4.6心肌组织ATP酶活性的测定：心肌组织匀浆后，用酶标仪以定磷法测定心肌组织匀浆液中ATP酶活性，包括Na+-K+-ATPase和Ca2+-Mg2+-ATPase。操作步骤遵循试剂盒说明书。
4.7心肌组织总腺苷和磷酸肌酸含量的测定：将配好的0.4mol/L高氯酸溶液预冷，然后放入心肌组织进行匀浆，低温离心(12000rpm，15min，4℃)后取上清液，用磷酸氢二钠溶液调节PH值至中性，于低温下再次15min离心取上清液，得到浓度为92.31mg/mL的心肌组织匀浆液。用高效液相色谱法测定心脏组织中的能量物质水平。使用的流动相A为甲醇－磷酸盐缓冲液(10mmol/L,pH＝6.2)，B为水/甲醇/乙腈(2:1:1，v/v/v)的混合溶液，采用梯度洗脱；检测波长为210nm、254nm；柱温为15℃；进样量为5μL。检测指标包括磷酸肌酸(phosphocreatine,PCr)、三磷酸腺苷(adenosine triphosphate,ATP)、二磷酸腺苷(asenosine diphosphate,ADP)和一磷酸腺苷(adenosine monophosphate,AMP)，并计算总腺嘌呤核苷酸(total adenine nucleotides,TAN,TAN＝ATP+ADP+AMP)及AMP/ATP比值。
4.8对心肌组织中AMPK-α2、PPAR-α和PGC-1α的mRNA表达的测定：心脏组织中总RNA的提取使用新鲜动物组织和细胞总RNA抽提试剂盒，使用2XComSYBR qPCR Mix(ROX+)试剂盒检测心肌组织中AMPK-α2、PPAR-α、PGC-1α和内参基因(Actb)的mRNA表达，所有操作遵循试剂盒说明书。实验中所使用的引物序列见下表：
表1 PCR引物序列
4.9统计分析方法：所有数据以均数±标准误的形式来表示。方差齐性者，采用单因素方差分析，组间两两比较使用LSD法，方差不齐者，采用秩和检验，使用SPSS 21.0软件统计，P<0.05视为具有统计学差异。
实验结果
1.空腹血糖水平 各组大鼠空腹血糖水平如表2所示。与正常对照组相比，模型组大鼠的空腹血糖水平明显升高(P<0.01)；与模型组相比，给药26天后，100mg/kg鱼腥草素钠组大鼠空腹血糖水平明显降低(P<0.01)。提示鱼腥草素钠有一定的降低血糖作用。
表2空腹血糖值(n＝8)
与正常组比,##P<0.01,与模型组比,**P<0.01.
2.血脂水平 各组大鼠的血脂水平如表3所示。与正常对照组相比，模型组大鼠血清中TG、TC、LDL-C和HDL-C水平显著升高(P<0.01)。给药治疗26天后，卡托普利能明显降低大鼠血清中TG和LDL水平(P<0.05，P<0.01)；50mg/kg和100mg/kg的鱼腥草素钠皆可降低大鼠血清中TG、TC、HDL和LDL水平(P<0.05，P<0.01)。表明鱼腥草素钠有明显降低血脂的作用。
表3血脂水平(n＝8)
与正常组比,##P<0.01,与模型组比,*P<0.05,**P<0.01.
3.对心肌损伤标志物的影响 与正常对照组相比，模型组大鼠血清中BNP含量显著升高，血清中ALT和AST的活性增加(P<0.01)；给药26天后，卡托普利及鱼腥草素钠皆可降低糖尿病引起的大鼠血清中BNP含量的升高(P<0.01)；卡托普利和50mg/kg鱼腥草素钠能降低糖尿病引起的血清中ALT和AST活性的升高(P<0.01，P<0.05)；100mg/kg鱼腥草素钠能降低大鼠血清中ALT的活性(P<0.05)。结果如表4所示。表明鱼腥草素钠可明显对抗心肌细胞的损伤。
表4血清心肌酶及生物标志物结果(n＝8)
与正常组比,##P<0.01,与模型组比,*P<0.05,**P<0.01.
4.心电图 如表5-1，5-2所示，实验末期，模型组大鼠心电图显示P-R、QRS波群、S-T和Q-T间期明显延迟(P<0.01)，且心率明显减慢(P<0.01)；给药治疗26天后，卡托普利和鱼腥草素钠皆可缩短糖尿病引起的P-R和QRS波群间期延迟(P<0.01)，并且能逆转糖尿病引起的心率减慢(P<0.01)。
表5-1心电图指标(n＝7～8)
与正常组比,#P<0.05,##P<0.01,与模型组比,**P<0.01.
表5-2心电图指标(n＝7～8)
与正常组比,##P<0.01,与模型组比,**P<0.01.
5.血清MDA含量 与正常对照组相比，模型组大鼠血清中MDA含量显著升高(P<0.01)；与模型组相比，在给药治疗26天后，卡托普利与鱼腥草素钠均能降低大鼠血清中MDA的含量(P<0.01),结果见表6。提示鱼腥草素钠可抑制糖尿病引起的过氧化。
表6血清MDA含量结果(n＝8)
与正常组比,##P<0.01,与模型组比,**P<0.01.
6.心肌组织ATP酶活性 实验结束时，模型组大鼠心肌组织中Na+-K+-ATPase和Ca2 +-Mg2+-ATPase活性明显低于正常对照组(P<0.01)；与模型组相比，在给药治疗26天后，卡托普利组和鱼腥草素钠50mg/kg剂量组的大鼠心肌组织中Ca2+-Mg2+-ATPase的活性增加(P<0.01，P<0.05)，Na+-K+-ATPase活性无明显变化，结果如表7所示。表明鱼腥草素钠通过对心肌线粒体的保护，对ATP酶活性的提高，改善心肌能量代谢。
表7心肌组织ATP酶活性(n＝8)
与正常组比,##P<0.01,与模型组比,**P<0.01.
7.心肌组织中能量物质水平 与正常组相比，在造模29天以后，模型组大鼠心肌组织中ATP、ADP、AMP、TAN和PCr的含量皆显著降低(P<0.01，P<0.05)；相比于模型组，经卡托普利治疗的大鼠心肌组织中ATP、ADP、TAN和PCr的含量皆显著升高(P<0.01)；50mg/kg剂量的鱼腥草素钠显著升高了大鼠心肌组织中ATP、ADP、TAN和PCr的含量(P<0.01)；100mg/kg剂量的鱼腥草素钠显著升高了大鼠心肌组织中ATP、ADP和TAN的含量(P<0.01)，并且，卡托普利组和鱼腥草素钠组的AMP/ATP比值显著降低(P<0.01)，结果见表8-1，8-2。表明鱼腥草素钠心肌能量代谢具有改善作用。
表8-1心肌组织中总腺苷和磷酸肌酸水平(n＝8)
与正常组比,#P<0.05,##P<0.01,与模型组比,**P<0.01.
表8-2心肌组织中总腺苷和磷酸肌酸水平(n＝8)
与正常组比,##P<0.01,与模型组比,**P<0.01.
8.对心肌组织中AMPK-α2、PPAR-α和PGC-1αmRNA表达的影响 与正常组相比，模型组大鼠的心肌组织中AMPK-α2和PGC-1αmRNA表达升高(P<0.05)；与模型组相比，卡托普利组和鱼腥草素钠100mg/kg剂量组大鼠的心肌组织AMPK-α2和PGC-1αmRNA表达降低(P<0.05)，鱼腥草50mg/kg剂量组大鼠心肌组织中AMPK-α2mRNA表达降低(P<0.05)。结果见表9。表明鱼腥草素钠通过调控AMPK信号通路来改善糖尿病引起心肌能量代谢紊乱从而对抗高血糖引起的心肌损伤乃至心衰。
表9心肌组织中AMPK-α2、PPAR-α和PGC-1α的mRNA相对表达水平
各组的mRNA相对表达量以相对于正常组表达量的倍数来表示。与正常组比,#P<0.05,与模型组比,*P<0.05.
总结
由上述实验结果表明：对于糖尿病心脏病模型大鼠，表现出高血糖、高血脂、血清心肌酶及氧化应激指标的异常、心率的减慢、心电图的异常、血清脑钠肽水平的升高；心肌能量代谢物质异常，表明糖尿病模型动物心肌损伤的发生，模型成功；心肌ATP酶活性降低，心肌AMPKα2、PGC-1αmRNA表达的升高，提示模型动物心肌线粒体受损及心肌AMPK通路出现表达升高。而经鱼腥草素钠干预后，血糖降低，氧化应激及血脂水平下降、心肌损伤、心脏功能有改善作用，鱼腥草素钠产生的这些效应是通过上调心肌ATP酶活性及下调AMP/ATP来调控AMPK通路，进而调控心肌能量代谢而达到，对于防治或延缓糖尿病心肌病的发生、发展，减少心糖尿病引起的心律失常、泵血功能降低等的发生率具有重要意义和应用价值。
本发明经实验证实：(1)鱼腥草素钠对糖尿病心脏病有防治作用，有心脏保护效果；(2)可调控心肌能量代谢紊乱；(3)可降低糖尿病引起血脂升高，有一定的降低血糖作用。在制备用于防治糖尿病引起的心脏损伤、心肌能量代谢紊乱、糖脂代谢异常等的产品方面具有良好的临床应用前景。
最后，需要在此指出的是：以上仅是本发明的实施例，只用于对本发明的技术方案作进一步详细地说明，不能理解为对本发明保护范围的限制，本领域的技术人员根据本发明的上述内容作出的一些非本质的改进和调整均属于本发明的保护范围。
Claims (6)
1.鱼腥草素钠在制备用于防治糖尿病心脏病产品中的应用。
2.鱼腥草素钠在制备防治糖尿病引起的血糖升高产品中的应用。
3.鱼腥草素钠在制备防治糖尿病引起的血脂升高及相关性疾病产品中的应用。
4.鱼腥草素钠在制备改善糖尿病引起的心肌能量代谢紊乱产品中的应用。
5.根据权利要求1～4之一所述的应用，其特征在于，产品包括药物、制剂或保健品中的一种。
6.根据权利要求1～4之一所述的应用，其特征在于，产品中还包括药学上或食品学上可接受的载体。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811325039.5A CN109223744A (zh) | 2018-11-08 | 2018-11-08 | 鱼腥草素钠在制备用于防治糖尿病心脏病产品中的应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811325039.5A CN109223744A (zh) | 2018-11-08 | 2018-11-08 | 鱼腥草素钠在制备用于防治糖尿病心脏病产品中的应用 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109223744A true CN109223744A (zh) | 2019-01-18 |
Family
ID=65077603
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811325039.5A Pending CN109223744A (zh) | 2018-11-08 | 2018-11-08 | 鱼腥草素钠在制备用于防治糖尿病心脏病产品中的应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109223744A (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110403997A (zh) * | 2019-08-30 | 2019-11-05 | 西安交通大学 | 一种鱼腥草提取物作为腺苷酸活化蛋白激酶激活剂在制备改善代谢综合征的药物中的应用 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108210487A (zh) * | 2018-03-02 | 2018-06-29 | 武汉科技大学 | 鱼腥草素钠在制备治疗心力衰竭和/或心律失常药物中的应用 |
-
2018
- 2018-11-08 CN CN201811325039.5A patent/CN109223744A/zh active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108210487A (zh) * | 2018-03-02 | 2018-06-29 | 武汉科技大学 | 鱼腥草素钠在制备治疗心力衰竭和/或心律失常药物中的应用 |
Non-Patent Citations (1)
| Title |
|---|
| 王海颖等: "鱼腥草改善糖尿病大鼠血脂代谢", 《中国中医基础医学杂志》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110403997A (zh) * | 2019-08-30 | 2019-11-05 | 西安交通大学 | 一种鱼腥草提取物作为腺苷酸活化蛋白激酶激活剂在制备改善代谢综合征的药物中的应用 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1429602B1 (en) | Methods for treating disorders using plant extracts | |
| Pliml et al. | Effects of ribose on exercise-induced ischaemia in stable coronary artery disease | |
| AU2002335689A1 (en) | Methods for treating disorders using plant extracts | |
| CN107441078B (zh) | 一种治疗糖尿病的药物组合物及其制备方法和用途 | |
| CN108042554B (zh) | 麦冬皂苷d在制备治疗代谢综合征药物上的应用 | |
| Ghalavand et al. | Effect of Exercise and Insulin Signaling on Glucose Transporter Type 4 in Skeletal Muscles: A narrative review | |
| EP2130533A1 (en) | Ataractic agent and functional food | |
| CN109223744A (zh) | 鱼腥草素钠在制备用于防治糖尿病心脏病产品中的应用 | |
| Henstridge et al. | Effects of the nitric oxide donor, sodium nitroprusside, on resting leg glucose uptake in patients with type 2 diabetes | |
| Suthar et al. | Efficacy and safety of PDM011011 capsules as compared to metformin in subjects with type-2 diabetes mellitus: An open-label, randomized, active-controlled, multicentric, phase III study | |
| US10849918B2 (en) | Composition for optic nerve protection | |
| EP1690519A1 (en) | Alpha-glucosidase activity inhibitor | |
| CN110464756A (zh) | 一种用于调节肥胖机体的葛根芩连汤水提取物 | |
| CN108619137B (zh) | 一种咔唑类化合物在制备治疗代谢性疾病及其并发症的药物中的应用 | |
| CN113768907A (zh) | 十七烷基间苯二酚在制备改善肌肉运动功能障碍产品中的应用 | |
| Oparinde et al. | Effect of Moringa oleifera leaf extract on serum lipids and glycaemic control in alloxan induced diabetic albino rats | |
| CN109200268A (zh) | 增重化合物的组合物及其长期使用方法 | |
| CN107019778A (zh) | 一种具有减肥和降血脂作用的组合物及其制备方法与用途 | |
| CN104968342B (zh) | 用于治疗或降低肝的胰岛素抵抗的莱菔硫烷 | |
| CN111249271A (zh) | 用于治疗糖尿病的药剂及其制备方法和应用 | |
| CN105055399A (zh) | 一种用于糖尿病防治的天然产物组合及其应用 | |
| CN111840331A (zh) | 一种熊胆外泌体在制备治疗ii型糖尿病药物中的应用 | |
| CN109481424A (zh) | 异甘草素、药物组合物及其在治疗糖尿病肾病中的应用 | |
| Hotta et al. | Effect of an aldose reductase inhibitor, SNK‐860, on deficits in the electroretinogram of diabetic rats | |
| CN108143756A (zh) | 一种植物降血糖药及其制备方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20190118 |
|
| RJ01 | Rejection of invention patent application after publication |