CN102727681A - Application of angelica peony powder in preparation of drugs for treating cirrhosis ascites - Google Patents
Application of angelica peony powder in preparation of drugs for treating cirrhosis ascites Download PDFInfo
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Abstract
The present invention provides an application of angelica peony powder in preparation of drugs for treating cirrhosis ascites. With the angelica peony powder of the present invention, indicators of TBIL, ALT and AST of cirrhosis ascites rats can be significantly reduced, ALB can be increased, A/G ratio inversion is improved, liver cell metabolism is improved, liver function is improved, and liver protection is achieved; and a liver fibrosis pathological state is improved, and pseudolobule formation is slowed so as to prevent cirrhosis formation. With combination of the angelica peony powder and V2 receptors of distal convoluted tubules and collecting ducts of kidney, water reabsorption of kidney collecting ducts is inhibited. In addition, with the angelica peony powder of the present invention, AQP4 expression in liver tissues is unregulated, ascites transportation is prompted, and cirrhosis ascites generation is reduced so as to provide treatment effects for cirrhosis ascites.
Description
Technical field
The present invention relates to a kind of medicine of treating cirrhotic ascites, specifically relate to the application of DANGGUI SHAOYAO SAN in preparation treatment cirrhotic ascites medicine.
Background technology
Liver cirrhosis is the late stage of various chronic hepatopathy development; Be, carrying out property chronic in the liver that liver causes, diffuse lesion by one or more reason long terms; Hepatocyte is extensively downright bad, and remaining hepatocyte forms regenerated nodule, connective tissue proliferation and fibrosis; Cause normal liver structural deterioration, pseudolobuli to form, cause liver function injury and portal hypertension.Liver cirrhosis early stage patient liver is in compensatory state, does not promptly get into the compensatory period of losing if do not add intervention, and patients ' life quality and survival rate will receive very big influence.Cirrhosis patients in decompensation patient about 75% is with ascites, and wherein about 15% patient is dead in 1 year, and 44% patients with ascites is dead in 2 years.
Mainly contain following three kinds of theories about the cirrhotic ascites mechanism: classical theory, the theory of overflowing and peripheral blood vessel distension theory.(1) classical theory: claim the underfilling theory again.Due to being broken mainly due to the balance between the colloid osmotic pressure difference between blood plasma and the ascites and portal vein blood capillary and the intraperitoneal liquid hydrostatic pressure reduction.Its mechanism is: 1. hypovolemia in the blood circulation causes that feritin, aldosterone produce too much water-sodium retention.2. liver cirrhosis makes the synthetic minimizing of albumin, causes hypoproteinemia.3. portal vein and sinus hepaticus increased pressure cause that the liquid hydrostatic pressing increases.4. because hepatic sinusoid pressure at both sides difference increases, liquid flows into the Disse gap by sinus hepaticus, forms too much lymph fluid.5. ascites forms the back because effective blood volume reduces, and feritin, Angiotensin II, aldosterone produce too much, cause water-sodium retention.6. pressure receptor is excited, and norepinephrine increases, sympathetic activation, and vasopressin (AVP) increases, and increases the weight of water-sodium retention.(2) theory of overflowing: mainly be because portal hypertension has activated the nerve fiber and the pressure receptor of blood sinus rich surrounding, strengthen the Liver and kidney neural reflex, sodium retention, the whole body blood volume increases, and liquid forms ascites by spilling in the internal organs circulation.(3) peripheral blood vessel distension theory: liver cirrhosis patient exists serious portal vein, blood sinus high pressure and hyperkinetic state, shows as blood pressure drops, Hypervolemia; High CO and vascular resistance reduce; The peripheral blood vessel expansion, little arteriovenous shunt causes blood volume and blood vessel capacity unbalance.Renin angiotensin aldosterone system occurs to the body reflexive and activate, sympathetic activation, vasopressin (AVP) increases, and water-sodium retention produces too much the lymph fluid of liver and internal organs, causes that liquid flows into the abdominal cavity.It is generally acknowledged, liver cirrhosis early, mid-term, it is main with the theory of overflowing that ascites forms mechanism, the later stage is main with the underfilling theory.
Arginine vasopressin (AVP) claim vasopressin, vassopressin again, produced by hypothalamic coker and the paraventricular nucleus cell looked, and is stored in neurohypophysis.The effect of AVP major physiological is to increase the heavily absorption of kidney to water, promptly brings into play antidiuretic activity.The main effect of AVP in the cirrhotic ascites morbidity can reduce: 1. the discharge minimizing of liver cirrhosis companion ascites, plasma AVP rising and solute free water is closely related, and AVP is high more, and solute free water is discharged few more; 2. in experimental Hepatocirrhosis Model, the AVP secretion increases and water output minimizing parallels; 3. confirm in experimental Hepatocirrhosis Model that aquaporin 2 (be AVP modulability aquaporin, mediation water is from the transportation of cell tubule side to capillary tube side) transport capacity strengthens; 4. confirmed that congenital AVP lacks rat water discharge obstacle can not take place; 5. use vaptans can recover the ability that most of liver cirrhosis companion hyponatremia patient kidney is discharged solute free water, correct hyponatremia, and it is relevant with the hyponatremia recurrence to discontinue medication.There is its special advantages in the corresponding with it AVP of being receptor antagonist class medicine in cirrhotic ascites treatment: (1) makes the absorption that the patient can strict restriction water; Thereby improving patients ' life quality. the discharge of urinating sodium can be reduced with conventional diuretic coupling in (2); Avoid the appearance of hyponatremia. along with the improvement of hyponatremia, the generation of hepatic encephalopathy will reduce (3). and improve hyponatremia before transplant (4) and can reduce transplanting back central nervous system complication.
In recent years, (for the formation of research cirrhotic ascites provides new angle, the transmembrane movement that experiment has confirmed the body hydrone has 90% to realize through AQP to aquaporin for aquaporin, discovery AQP), only 10% realizes through dispersion.CBV and blood vessel capacity reduced when the pathogenesis of hepatic ascites possibly be liver cirrhosis, and reflexive ground activates renin angiotensin aldosterone system, sympathetic activation; Arginine vasopressin (AVP) secretion increasing; AVP and kidney V2 receptors bind, (aquaporin-2 AQP2) opens to make the epithelial AVP dependency of kidney distal tubule and collecting tubule aquaporin-aquaporin 2; Cause the kidney collecting tubule to heavily absorption increase, the portal venous pressure of water increase, the Secondary cases aldosterone increases; Kidney heavily absorbs increase to water, sodium, thereby causes water-sodium retention, forms ascites.
Modern medicine then is to regulate water, sodium balance to the therapeutic strategy of hepatic ascites at present, is principle with the diuresis of limit sodium, corrects the circulatory function disorder.Difficultly curing ascites is normal to adopt portosystemic shunt and liver transplantation etc. in the tapping of a large amount of abdominal cavities and expanding blood volume, self concentrated ascites reinfusion, peritoneovenous shunt, the jugular vein liver.Though above-mentioned treatment means is effective in cure with technology, owing to meeting causes reasons such as new damage and liver transplantation cost height to the patient, has more drawback.
In view of this; The present invention is based on the Chinese medicine traditional theory; From cirrhotic ascites pathogenesis and approach such as AVP and AQP, the application of a kind of DANGGUI SHAOYAO SAN in preparation treatment cirrhotic ascites medicine is provided, in the cirrhotic ascites treatment, show special advantages.
Summary of the invention
Of the present invention the application of a kind of DANGGUI SHAOYAO SAN in preparation treatment cirrhotic ascites medicine be provided; DANGGUI SHAOYAO SAN can obviously reduce cirrhotic ascites rat TBIL, ALT, AST index; Rising ALB and improve the A/G ratio and be inverted; Can improve hepatocellular metabolism, improve liver function, realize hepatoprotective; Improve the liver cirrhosis pathology state, alleviate pseudolobuli and form, and then prevent the formation of liver cirrhosis; DANGGUI SHAOYAO SAN through with kidney Distal convoluted tubule, collecting tubule V2 receptors bind, suppress of the heavily absorption of kidney collecting tubule to water; Improve the expression of hepatic tissue AQP4, promote transhipment, reduce cirrhotic ascites and generate, and then reach therapeutical effect cirrhotic ascites to ascites.
The present invention realizes through following technical scheme:
The application of a kind of DANGGUI SHAOYAO SAN in preparation treatment cirrhotic ascites medicine, said DANGGUI SHAOYAO SAN is the oral formulations by the adjuvant processing of 2～4 weight portion Radix Angelicae Sinensis, 14～18 weight portion Radix Paeoniaes, 6～10 weight portion Rhizoma Chuanxiongs, 3～5 weight portion Rhizoma Atractylodis Macrocephalaes, 3～5 weight portion Poria, 6～10 weight portion Rhizoma Alismatis and pharmaceutically permission.
Preferably, said DANGGUI SHAOYAO SAN is the oral formulations by the adjuvant processing of 3 weight portion Radix Angelicae Sinensis, 16 weight portion Radix Paeoniaes, 8 weight portion Rhizoma Chuanxiongs, the 4 weight portion Rhizoma Atractylodis Macrocephalaes, 4 weight portion Poria, 8 weight portion Rhizoma Alismatis and pharmaceutically permission.
Preferably, said oral formulations is oral liquid, powder, capsule, granule or tablet.
Preferably, said adjuvant is selected from one or more in starch, dextrin, lactose, amylum pregelatinisatum, microcrystalline Cellulose, inorganic salt and the mannitol.
Preferably, said inorganic salt is selected from calcium sulfate, calcium hydrogen phosphate and the medicinal calcium carbonate one or more.
DANGGUI SHAOYAO SAN can obviously reduce cirrhotic ascites rat TBIL, ALT, AST index, and rising ALB and improve the A/G ratio and be inverted explain that DANGGUI SHAOYAO SAN can improve hepatocellular metabolism, improves liver function, the realization hepatoprotective; DANGGUI SHAOYAO SAN can improve the liver cirrhosis pathology state, alleviates pseudolobuli and forms, and then prevent the formation of liver cirrhosis; DANGGUI SHAOYAO SAN through with kidney Distal convoluted tubule, collecting tubule V2 receptors bind, suppress of the heavily absorption of kidney collecting tubule to water; DANGGUI SHAOYAO SAN promotes the transhipment to ascites through improving the expression of hepatic tissue AQP4, reduces cirrhotic ascites and generates, and then reach the therapeutical effect to cirrhotic ascites.
Description of drawings
Fig. 1 is the figure as a result of 10 * 40 times of normal rats hepatic tissue HE dyeing.
Fig. 2 is the figure as a result of 10 * 40 times of model group liver tissues of rats pathology HE dyeing.
Fig. 3 is the figure as a result of 10 * 40 times of positive group liver tissues of rats pathology HE dyeing.
Fig. 4 is the figure as a result of 10 * 40 times of DANGGUI SHAOYAO SAN low dose group liver tissues of rats pathology HE dyeing.
Fig. 5 is the figure as a result of 10 * 40 times of DANGGUI SHAOYAO SAN high dose group liver tissues of rats pathology HE dyeing.
Fig. 6 is the figure as a result of 10 * 40 times of normal rats hepatic tissue AQP4 dyeing.
Fig. 7 is the figure as a result of 10 * 40 times of model group liver tissues of rats AQP4 dyeing.
Fig. 8 is the figure as a result of 10 * 40 times of DANGGUI SHAOYAO SAN high dose group liver tissues of rats AQP4 dyeing.
Fig. 9 is the figure as a result of 10 * 40 times of DANGGUI SHAOYAO SAN low dose group liver tissues of rats AQP4 dyeing.
Figure 10 is the figure as a result of 10 * 40 times of positive group liver tissues of rats AQP4 dyeing.
The specific embodiment
Elaborate in the face of embodiments of the invention down, present embodiment provided detailed embodiment and concrete operating process, but protection scope of the present invention is not limited to following embodiment being to implement under the prerequisite with technical scheme of the present invention.
The Radix Angelicae Sinensis that the present invention adopted, Radix Paeoniae, Rhizoma Chuanxiong, the Rhizoma Atractylodis Macrocephalae, Poria, Rhizoma Alismatis be available from medicine Hefei, Nanjing TianXing pharmaceuticals, and meet down standard of the Pharmacopoeia of the People's Republic of China (version in 2010); Carbon tetrachloride (analytical pure) is available from Jiangsu Qiangsheng Chemical Co., Ltd.; Good fortune near the house the one-level Oleum Brassicae campestris available from East Sea grain and oil Industrial Co., Ltd of China Oil and Food Import and Export Corporation; Formaldehyde (analytical pure) is available from Shanghai pilot scale chemical corp; The AVP enzyme is exempted from test kit available from Shanghai happy bio tech ltd alive; Diammonium glycyrrhizinate is available from Jiangsu Zhengda Tianqing Drug Industry Co., Ltd.
The animal that the present invention uses is to be the SD male rat of 220 ± 20g by west, the Shanghai body weight that pul-Bi Kai laboratory animal company limited provides; Its quality certification number is SCXK (Shanghai) 2003-0002; All normally raise a week (free diet before each treated animal experiment at laboratory; Drinking-water is fed the standard particle feedstuff, room temperature 18-22 ℃).
The electronic balance that the present invention uses is available from Beijing match Doris limited company, and model is Sartorius BS110S; The centrifugation device is available from Shanghai operating theater instruments two factories, and model is 800 types; Tianjin, island automatic clinical chemistry analyzer is available from Olympus company; JEOL21230 type Electronic Speculum (Japan); LKB2NOVA type microtome (Sweden).
Embodiment 1 preparation medical material extractum
According to Radix Angelicae Sinensis 2 weight portions, Radix Paeoniae 18 weight portions, Rhizoma Chuanxiong 6 weight portions, the Rhizoma Atractylodis Macrocephalae 5 weight portions; Poria 3 weight portions, Rhizoma Alismatis 10 weight portions and the adjuvant weighing medical material that pharmaceutically allows add 10 times of 50% ethanol to the medical material gross weight; Soak 60min, water-bath backflow 1.5h, filtrating is collected in the cooling back; Add 8 times of 50% ethanol water-bath backflow 1.5h to the medical material gross weight again, filtrating is collected in the cooling back.Merge filtrating twice, filter, reclaim ethanol to there not being the alcohol flavor, water-bath is concentrated into extractum, and vacuum drying promptly gets DANGGUI SHAOYAO SAN.
Embodiment 2 preparation medical material extractum
According to Radix Angelicae Sinensis 3 weight portions, Radix Paeoniae 16 weight portions, Rhizoma Chuanxiong 8 weight portions, the Rhizoma Atractylodis Macrocephalae 4 weight portions; Poria 4 weight portions, Rhizoma Alismatis 8 weight portions and the adjuvant weighing medical material that pharmaceutically allows add 10 times of 50% ethanol to the medical material gross weight; Soak 60min, water-bath backflow 1.5h, filtrating is collected in the cooling back; Add 8 times of 50% ethanol water-bath backflow 1.5h to the medical material gross weight again, filtrating is collected in the cooling back.Merge filtrating twice, filter, reclaim ethanol to there not being the alcohol flavor, water-bath is concentrated into extractum, and vacuum drying promptly gets DANGGUI SHAOYAO SAN.
Embodiment 3 preparation medical material extractum
According to Radix Angelicae Sinensis 4 weight portions, Radix Paeoniae 14 weight portions, Rhizoma Chuanxiong 10 weight portions, the Rhizoma Atractylodis Macrocephalae 3 weight portions; Poria 5 weight portions, Rhizoma Alismatis 6 weight portions and the adjuvant weighing medical material that pharmaceutically allows add 10 times of 50% ethanol to the medical material gross weight; Soak 60min, water-bath backflow 1.5h, filtrating is collected in the cooling back; Add 8 times of 50% ethanol water-bath backflow 1.5h to the medical material gross weight again, filtrating is collected in the cooling back.Merge filtrating twice, filter, reclaim ethanol to there not being the alcohol flavor, water-bath is concentrated into extractum, and vacuum drying promptly gets DANGGUI SHAOYAO SAN.
Embodiment 4 sets up cirrhotic ascites animal model and administration
75 male SD rats are divided into 7 groups at random: normal group (10), model group (20), the heavy dose of group of DANGGUI SHAOYAO SAN (15), DANGGUI SHAOYAO SAN small dose group (15), positive controls (15, diammonium glycyrrhizinate).
Tested for first week, except that normal group, other each groups are induced as drinking water with 35% phenobarbital solution.From second week, except that normal group, all the other groups all adopt following intraperitoneal injection: second week: 13% carbon tetrachloride solution, and the 3rd week: 16% carbon tetrachloride solution, around the: 20% carbon tetrachloride solution, the 5th thoughtful the tenth week: 25% carbon tetrachloride solution.Lumbar injection is 2 times weekly, 0.1mL/100g.Experiment the last fortnight gives mixed feed, gives normal diet afterwards.The method that the present invention adopts carbon tetrachloride associating phenobarbital to bring out the cirrhotic ascites model.Because phenobarbital is the liver drug enzyme derivant, can promote the synthetic of Cytochrome P450, thereby the metabolism of quickening carbon tetrachloride increases the weight of liver toxicity, has shortened the time of simple use tetrachloro-methane induction cirrhotic ascites.Rat after 35% phenobarbital is induced a week, carbon tetrachloride oil solution lumbar injection continuous 10 all reproducible cirrhotic ascites models, and model group ascites volume, liver function index all have significant difference than normal group difference.
DANGGUI SHAOYAO SAN low dose group, high dose group dosage are respectively 3.9g/kg, 7.8g/kg (being equivalent to crude drug 14.8g/kg, 29.6g/kg); Diammonium glycyrrhizinate: 26.25mg/kg; Normal group and model group wait the dosage distilled water.From setting up model beginning in first day gastric infusion, 1 time/day, irritating stomach dosage is 1mL/100g, continuous ten weeks.The tenth weekend, fasting 12h after the administration, abdominal aortic blood is also gathered the hepatic tissue BIAO and BEN.
Embodiment 5 indexs detect and interpretation of result
1, index detection method
(1) seroperitoneum amount: the difference of weight was assessed before and after ascites volume can be placed in the abdominal cavity with filter paper.Behind the rat anesthesia, 1.5cm is cut off in the abdominal cavity, and the filter paper of will weighing is filled in the abdominal cavity rapidly, and filter paper fully absorbs the seroperitoneum taking-up after 3 minutes, claims that filter paper is heavy, calculates seroperitoneum weight.
(2) serum liver function: behind the rat anesthesia, abdominal aortic blood, the blood room temperature was placed after 30 minutes; Centrifugal 15min, rotating speed 3500r/min, separation of serum; Put-20 ℃ of preservations, full-automatic biochemical detector for use detects ALT, AST, TBIL, ALB and A/G index of correlation.
(3) AVP of liver tissue homogenate assay: from the same leaf of liver, clip 50mg liver, the ice normal saline is cleaned, and shreds; Put homogenizer, add the ice normal saline of 0.5mL, grind homogenate, process liver homogenate; Leave standstill 2500r/min, 4 ℃ of centrifugal 10min; Get supernatant, place-20 ℃ of preservations, ELISA is measured AVP content.
(4) liver organization morphological observation: liver is drawn materials with leaf, and pruning is back to be fixed with 10% formalin.Make the pathology paraffin section, carry out hematoxylin-eosin (HE) dyeing, observe and take the photograph phase under the optical microscope.
(5) hepatic tissue aquaporin 4 (AQP4) is expressed: the hepatic tissue BIAO and BEN is fixed with 10% formalin, FFPE, and 5 μ m serial section are carried out immunohistochemical staining.Behind the paraffin section gradient ethanol eluting, 3%H
20
2Hatch 20min, eliminate the endogenous catalase activity; Microwave is repaired antigen 1 0min; Drip NIS, incubated at room 20min discards unnecessary serum; Drip 1: 100 one anti-4 ℃ spend the night, 37 ℃ of rewarmings 45 minutes, PBS are given a baby a bath on the third day after its birth times each 2 minutes; It is anti-to drip biotinylation two, room temperature 20 minutes; PBC wash 2 times each 5 minutes; Drip reagent SABC, room temperature 20 minutes; PBS wash 2 times each 5 minutes; The DAB colour developing; 2 minutes, hydrochloride alcohol differentiation are redyed in distillation washing, haematoxylin; Dehydration, transparent, mounting, microscopy.With cell membrane and Cytoplasm the pale brown color positive cell that dyes is arranged; All sections are observed under optical microscope; Well (positive cell dyeing is clear to get dyeing; Background dyeing is very low) tissue slice take a picture, and the application cell image analysis system is measured the expression that the gray value method detects AQP4.
(6) statistical procedures: all (x ± s) expression adopts one factor analysis of variance to the continuous variable, uses SPSS10.0 software and carries out statistical procedures with mean ± standard deviation.
2, interpretation of result
(1) to the influence of rats with liver cirrhosis seroperitoneum
Model group and normal group compare, and the seroperitoneum amount obviously raises, and difference has remarkable statistical significance (P＜0.01), explain that the inductive Hepatocirrhosis Model of carbon tetrachloride associating phenobarbital can finally form ascites.DANGGUI SHAOYAO SAN high dose group, DANGGUI SHAOYAO SAN low dose group, positive group rat abdominal cavity hydrops amount all decrease than model group, and difference has statistical significance (P＜0.05).DANGGUI SHAOYAO SAN is as shown in table 1 to the influence (
n=10) of cirrhotic ascites rat model seroperitoneum.
Table 1
| Group | Dosage (g/kg) | Seroperitoneum amount (g) |
| Normal group | 0.152±0.076 | |
| Model group | 0.300±0.129 ▲▲ | |
| Positive group | 2.65×10 -2 | 0.198±0.051 * |
| Low dose group | 3.9 | 0.186±0.083 * |
| High dose group | 7.8 | 0.177±0.122 * |
Annotate:
*P＜0.05,
*P＜0.01vs model group; ▲ P＜0.05, ▲ ▲ P＜0.01vs normal group
Experiment shows model group and compared with normal, and seroperitoneum significantly raises, and explains that the Hepatocirrhosis Model of tetrachloro-methane induction finally forms ascites.The seroperitoneum that DANGGUI SHAOYAO SAN high and low dose group all can reduce the cirrhotic ascites rat generates.
(2) to the influence of cirrhotic ascites rat ALT, AST, TBIL, ALB, A/G
Model group and compared with normal, ALT, AST, TBIL index raise, and difference has statistical significance (P＜0.05), and liver function damage is described.DANGGUI SHAOYAO SAN administration group rat ALT, AST, TBIL index all reduce, and difference has statistical significance (P＜0.05).Model group and compared with normal, ALB, A/G reduce, and difference has statistical significance (P＜0.05), and model group rat liver chronic injury is described.DANGGUI SHAOYAO SAN high dose group can significantly raise ALB, the A/G index of cirrhotic ascites rat, difference has statistical significance (P＜0.01).Other each administration groups and model group relatively have remarkable significant difference (P＜0.01 or P＜0.05).Explain that DANGGUI SHAOYAO SAN can improve cirrhotic ascites rats'liver function.DANGGUI SHAOYAO SAN is as shown in table 2 to the influence (n=10,
) of cirrhotic ascites ALT, AST, TBIL, ALB, A/G.
Table 2
Annotate:
*P＜0.05,
*P＜0.01vs model group; ▲ P＜0.05, ▲ ▲ P＜0.01vs normal group
Result of study of the present invention shows: model group and compared with normal, TBIL, ALT, AST index all raise and statistical significance (P＜0.01, P＜0.05), the rat liver function damage of tetrachloro-methane induction in the illustrative experiment are all arranged.Each administration group all can reduce TBIL in the cirrhotic ascites rat blood serum, ALT, AST index.
Among the present invention; Model group is compared with blank control group, and ALB, A/G index reduce, and difference has statistical significance (P＜0.05); The rat liver function that tetrachloro-methane induction is described is impaired; The ALB reduction that each administration group all can raise and cause because of cirrhotic ascites, and then cause that plasma colloid osmotic pressure raises, thus alleviate edema.The A/G ratio of cirrhotic ascites model group is inverted, and reflected liver function damage, and each administration group all has improvement, shows that DANGGUI SHAOYAO SAN can change hepatocyte albumin content and albumins/globulins (A/G) ratio, and then changes colloid osmotic pressure, alleviates edema.
(3) to the influence of AVP content in the cirrhotic ascites rat liver
AVP content obviously raises in normal group in the cirrhotic ascites rat model group liver, has significant difference (P＜0.05); AVP content all reduces in DANGGUI SHAOYAO SAN high dose group and the positive group rat liver, relatively has diversity (P＜0.05) with model group.DANGGUI SHAOYAO SAN is as shown in table 3 to the influence (
n=10) of AVP content in the cirrhotic ascites rat liver.
Table 3
| Group | Dosage (g/kg) | AVP(ng/L) |
| Normal group | - | 93.670±11.619 |
| Model group | - | 105.272±10.016 ▲ |
| Positive group | 2.65×10 -2 | 91.200±14.585 * |
| Low dose group | 3.9 | 101.880±13.507 |
| High dose group | 7.8 | 85.633±19.484 * |
Annotate:
*P＜0.05,
*P＜0.01vs model group; ▲ P＜0.05, ▲ ▲ P＜0.01vs normal group
(4) to the pathological influence of cirrhotic ascites rat
The HE demonstration of dyeing, normal group liver lobules of liver structural integrity, hepatocyte is arranged and forms liver plate, no degeneration necrosis, portal area NIP cellular infiltration.The structural deterioration of model group liver lobules of liver is serious, hepatic cords arrangement disorder, the hepatocellular degeneration necrosis that sporadically appears, inflammatory cell infiltrations such as visible mononuclear cell and lymphocyte in portal area and the necrosis region.Compare with model group; DANGGUI SHAOYAO SAN administration group hepatic necrosis reduces, and the portal area inflammatory cell infiltration also alleviates than model group, and the prompting DANGGUI SHAOYAO SAN can improve the Fibrotic degree of cirrhotic ascites rat liver; And then influence pseudolobuli formation, thereby treatment cirrhotic ascites.Each organizes liver tissues of rats pathological change situation such as Fig. 1, Fig. 2, Fig. 3, Fig. 4 and shown in Figure 5.
(5) influence of AQP4 in the cirrhotic ascites rat liver being expressed
Under 10 * 10 times of visuals field, observe every section cell membrane, cytoplasm and be the positive expression of clear pale brown color.The visual field of 5 non-overlapping copies of picked at random, regional to positive expression under 10 * 40 times of visuals field again, carry out density scan through image analysis system, add up average optical density value in each visual field.Can know that in conjunction with Fig. 6 to Figure 10 and table 4 all section statining backgrounds are clear, the AQP4 positive reaction is fallow, mainly is present in cell membrane, Cytoplasm and stroma.The AQP4 expression that is positive in the normal group liver bile duct endotheliocyte, model group are expressed obviously and are reduced, and the DANGGUI SHAOYAO SAN low dose group is expressed obviously than model group AQP4 and strengthened.Dangguishaoyao San on rat liver cirrhosis average optical density of AQP4 (
n = 10) shown in Table 4.
Table 4
Annotate:
*P＜0.05,
*P＜0.01vs model group; ▲ P＜0.05, ▲ ▲ P＜0.01vs normal group
Can know from the foregoing description:
DANGGUI SHAOYAO SAN can obviously reduce cirrhotic ascites rat TBIL, ALT, AST index, and rising ALB and improve the A/G ratio and be inverted explain that DANGGUI SHAOYAO SAN can improve hepatocellular metabolism, improves liver function, the realization hepatoprotective;
DANGGUI SHAOYAO SAN can improve the liver cirrhosis pathology state, alleviates pseudolobuli and forms, and then prevent the formation of liver cirrhosis;
DANGGUI SHAOYAO SAN through with kidney Distal convoluted tubule, collecting tubule V2 receptors bind, suppress of the heavily absorption of kidney collecting tubule to water; Improve the expression of hepatic tissue AQP4, promote transhipment, reduce cirrhotic ascites and generate, and then reach therapeutical effect cirrhotic ascites to ascites.
Claims (5)
1. the application of DANGGUI SHAOYAO SAN in preparation treatment cirrhotic ascites medicine, it is characterized in that: said DANGGUI SHAOYAO SAN is the oral formulations by the adjuvant processing of 2～4 weight portion Radix Angelicae Sinensis, 14～18 weight portion Radix Paeoniaes, 6～10 weight portion Rhizoma Chuanxiongs, 3～5 weight portion Rhizoma Atractylodis Macrocephalaes, 3～5 weight portion Poria, 6～10 weight portion Rhizoma Alismatis and pharmaceutically permission.
2. the application of DANGGUI SHAOYAO SAN according to claim 1 in preparation treatment cirrhotic ascites medicine is characterized in that: said DANGGUI SHAOYAO SAN is the oral formulations by the adjuvant processing of 3 weight portion Radix Angelicae Sinensis, 16 weight portion Radix Paeoniaes, 8 weight portion Rhizoma Chuanxiongs, the 4 weight portion Rhizoma Atractylodis Macrocephalaes, 4 weight portion Poria, 8 weight portion Rhizoma Alismatis and pharmaceutically permission.
3. the application of DANGGUI SHAOYAO SAN according to claim 1 and 2 in preparation treatment cirrhotic ascites medicine, it is characterized in that: said oral formulations is oral liquid, powder, capsule, granule or tablet.
4. the application of DANGGUI SHAOYAO SAN according to claim 1 and 2 in preparation treatment cirrhotic ascites medicine, it is characterized in that: said adjuvant is selected from one or more in starch, dextrin, lactose, amylum pregelatinisatum, microcrystalline Cellulose, inorganic salt and the mannitol.
5. the application of DANGGUI SHAOYAO SAN according to claim 4 in preparation treatment cirrhotic ascites medicine is characterized in that: said inorganic salt is selected from calcium sulfate, calcium hydrogen phosphate and the medicinal calcium carbonate one or more.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104825693A (en) * | 2015-04-16 | 2015-08-12 | 成都市飞龙水处理技术研究所青白江第一分所 | Decoction medicine for treating pregnant sciatica, and preparation method thereof |
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| CN105616769A (en) * | 2016-01-07 | 2016-06-01 | 青岛辰达生物科技有限公司 | Pharmaceutical preparation for treating ascites due to cirrhosis |
| CN116920030A (en) * | 2023-05-16 | 2023-10-24 | 海南医学院第二附属医院 | Traditional Chinese medicine composition for treating diabetic peripheral neuropathy qi deficiency and blood stasis |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104825693A (en) * | 2015-04-16 | 2015-08-12 | 成都市飞龙水处理技术研究所青白江第一分所 | Decoction medicine for treating pregnant sciatica, and preparation method thereof |
| CN105106345A (en) * | 2015-10-10 | 2015-12-02 | 王伟 | Medicine and therapy for ascites due to cirrhosis |
| CN105106345B (en) * | 2015-10-10 | 2018-08-10 | 王伟 | A kind of drug for treating cirrhotic ascites |
| CN105616769A (en) * | 2016-01-07 | 2016-06-01 | 青岛辰达生物科技有限公司 | Pharmaceutical preparation for treating ascites due to cirrhosis |
| CN116920030A (en) * | 2023-05-16 | 2023-10-24 | 海南医学院第二附属医院 | Traditional Chinese medicine composition for treating diabetic peripheral neuropathy qi deficiency and blood stasis |
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