CN115350174B - Application of L-norvaline in preparing medicines for treating ventricular remodeling after myocardial infarction - Google Patents
Application of L-norvaline in preparing medicines for treating ventricular remodeling after myocardial infarction Download PDFInfo
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- CN115350174B CN115350174B CN202211195776.4A CN202211195776A CN115350174B CN 115350174 B CN115350174 B CN 115350174B CN 202211195776 A CN202211195776 A CN 202211195776A CN 115350174 B CN115350174 B CN 115350174B
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Classifications
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- 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
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- 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
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
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- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Cardiology (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Epidemiology (AREA)
- Hospice & Palliative Care (AREA)
Abstract
The invention provides an application of L-norvaline in preparing a medicine for treating ventricular remodeling after myocardial infarction, and relates to the technical field of biological medicines. The invention is found by experimental study of a mouse animal model: l-norvaline can improve cardiac function of Myocardial Infarction (MI) mice, inhibit myocardial hypertrophy of the MI mice, and reduce myocardial apoptosis of the MI mice. The invention makes clear for the first time that the L-norvaline can improve ventricular remodeling and heart failure caused by myocardial infarction, provides a new drug development path and drug action target point for treating ventricular remodeling and heart failure caused by myocardial infarction, and has very important medicinal value.
Description
Technical Field
The invention relates to the technical field of biological medicines, in particular to application of L-norvaline in preparing a medicine for treating ventricular remodeling after myocardial infarction.
Background
Myocardial infarction (Myocardial infarction, MI) is myocardial necrosis due to acute and persistent ischemia and hypoxia of the coronary arteries. The myocardial infarction is sudden in onset and high in death rate, and is one of serious diseases seriously endangering the life and health of human beings. Along with the development of treatment means such as direct coronary intervention (PCI) treatment, thrombolytic treatment and the like, the acute-phase mortality rate of myocardial infarction is greatly reduced, but pathological ventricular remodeling and heart failure which occur after myocardial infarction still bring great burden to a medical support system. Therefore, the continuous optimization of drug treatment schemes, and the search for the occurrence mechanism of heart failure caused by myocardial infarction has positive significance in treating cardiovascular diseases.
Intestinal microorganisms play an important regulatory role in human health and in the development and progression of diseases. In recent years, there has been growing evidence that changes in intestinal microorganisms are associated with a variety of diseases including obesity, type ii diabetes, fatty liver, hypertension, heart failure and myocardial infarction. We have found in early studies that L-norvaline (L-Norvaline) is a metabolite in serum associated with intestinal microorganisms. Another study found that L-norvaline was lower in intestinal metabolites in breast cancer patients than in healthy subjects, and further studies showed that L-norvaline was able to inhibit proliferation activity of breast cancer cells. Faeces from vaginally delivered infants are reported to be associated with high abundance of DL-norvaline, which is significantly positively correlated with the intestinal probiotic bifidobacteria. In addition, L-norvaline is a pharmaceutical intermediate of perindopril, ACE-inhibitors, antihypertensive agents. However, there is no research and invention concerning treatment of heart failure caused by myocardial infarction by L-norvaline.
Disclosure of Invention
The invention aims to provide an application of L-norvaline in preparing a medicine for treating ventricular remodeling after myocardial infarction, wherein the L-norvaline can improve cardiac dysfunction caused by myocardial infarction, improve myocardial cell hypertrophy caused by myocardial infarction and reduce myocardial cell apoptosis caused by myocardial infarction.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides an application of L-norvaline in preparing a medicine for treating ventricular remodeling after myocardial infarction.
Preferably, the myocardial infarction comprises cardiovascular disease induced myocardial infarction.
Preferably, the L-norvaline improves cardiac dysfunction caused by myocardial infarction.
Preferably, the L-norvaline improves myocardial cell hypertrophy caused by myocardial infarction.
Preferably, the L-norvaline reduces myocardial apoptosis caused by myocardial infarction.
The invention provides a medicine for treating ventricular remodeling after myocardial infarction, and the effective components of the medicine comprise L-norvaline and pharmaceutically acceptable auxiliary materials.
Preferably, the adjuvant comprises a diluent, buffer, suspension, emulsion, granule, encapsulating agent, excipient, filler, binder, spray, transdermal absorbent, wetting agent, disintegrant, absorption enhancer, surfactant, colorant, flavoring agent, or adsorption carrier.
Preferably, the dosage form of the medicine comprises tablets, powder, granules, capsules, decoction, oral liquid, injection or suppositories.
Compared with the prior art, the invention has the following effects:
The invention provides an application of L-norvaline in preparing a medicine for treating ventricular remodeling after myocardial infarction. Animal experiments show that the L-norvaline can improve cardiac dysfunction caused by myocardial infarction, improve myocardial cell hypertrophy caused by myocardial infarction and reduce myocardial cell apoptosis caused by myocardial infarction. The invention makes clear for the first time that the L-norvaline can improve heart failure caused by myocardial infarction, provides a new drug development path and drug action target point for treating heart failure and ventricular remodeling caused by myocardial infarction, and has very important medicinal value.
Drawings
FIG. 1 is a representation of cardiac ultrasound following administration by lavage in a Myocardial Infarction (MI) mouse; wherein A: and (2) gastric lavage administration of normal saline, B: l-norvaline is administered by intragastric administration.
FIG. 2 is a graph of statistics of left ventricular ejection fraction (EF,%) and left ventricular short axis shortening fraction (FS,%) of mouse cardiac ultrasound; wherein p <0.001.
Fig. 3 is a representative view of hematoxylin-eosin (HE) stained heart cross-sections of Myocardial Infarction (MI) mice following administration by gavage, wherein a: and (2) gastric lavage administration of normal saline, B: l-norvaline is administered by intragastric administration.
FIG. 4 is a cell size statistic of hematoxylin-eosin (HE) stained myocardial cross-section; wherein p <0.001.
Fig. 5 is a representation of malt lectin (WGA) stained heart cross section after administration by gavage in a Myocardial Infarction (MI) mouse, wherein a: and (2) gastric lavage administration of normal saline, B: l-norvaline is administered by intragastric administration.
FIG. 6 is a cell size statistic of malt lectin (WGA) stained myocardial cross section; wherein p <0.001.
FIG. 7 is a Western blot analysis of Bax and Bcl 2 protein expression in heart tissue of Myocardial Infarction (MI) mice administered by gastric lavage with saline and L-norvaline, respectively.
FIG. 8 is a statistical result of Bax/Bcl 2 protein expression; wherein p <0.01.
Detailed Description
The invention provides an application of L-norvaline in preparing a medicine for treating ventricular remodeling after myocardial infarction. In the present invention, the source of the L-norvaline is not particularly limited. In a specific embodiment of the invention, the L-norvaline reagent is purchased from Sigma, cat: N7627-10G. As one embodiment, a solution of L-norvaline at a desired concentration is prepared using physiological saline.
In the present invention, the myocardial infarction includes cardiovascular disease-induced myocardial infarction.
In the present invention, the L-norvaline improves cardiac dysfunction caused by myocardial infarction. Cardiac dysfunction is also known as cardiac insufficiency or heart failure, and myocardial infarction results in ischemic heart failure. The research of the invention shows that: after L-norvaline is administered to Myocardial Infarction (MI) mice by means of gastric lavage for 8 weeks, the left ventricular Ejection Fraction (EF) and the left ventricular short axis reduction Fraction (FS) are measured, and compared with the normal saline mice administered by gastric lavage, the left ventricular Ejection Fraction (EF) and the left ventricular short axis reduction Fraction (FS) of the mice treated by the method are obviously improved, so that the cardiac function of the mice can be improved by L-norvaline administration.
In the present invention, the L-norvaline improves myocardial cell hypertrophy caused by myocardial infarction. According to the invention, the H & E staining is used for detecting the cross-sectional area of the myocardial cells, and experimental results show that the myocardial cells of the mice in the normal saline gastric lavage administration group are obviously larger, and the myocardial cells of the mice are obviously reduced after the L-norvaline is treated, so that the L-norvaline can improve the pathologic myocardial hypertrophy of the mice with Myocardial Infarction (MI). According to the invention, myocardial tissue of a Myocardial Infarction (MI) model mouse is analyzed through malt lectin (WGA) staining, the result is consistent with the H & E staining detection result, myocardial cells of a normal saline lavage administration group mouse are obviously larger, and after L-norvaline treatment, the myocardial cells of the mouse are obviously reduced, so that the L-norvaline can improve pathological myocardial hypertrophy of the MI mouse.
In the present invention, the L-norvaline reduces myocardial apoptosis caused by myocardial infarction. Apoptosis occurs in close association with the expression level of the Bax/Bcl 2 pair of apoptosis-controlling genes. According to the invention, a Western immunoblotting (Western Blotting) detection research result shows that after the Myocardial Infarction (MI) model mouse is dosed with L-norvaline for 8 weeks, the Bax protein expression is reduced, the Bcl 2 protein expression is increased, the Bax/Bcl 2 ratio is reduced, and fewer apoptotic myocardial cells and injury are indicated. And after the normal saline is used for lavage of mice with a dosing model, the Bax protein expression is obviously increased, the Bcl 2 protein expression is obviously reduced, the Bax/Bcl 2 ratio is obviously increased, and the apoptosis myocardial cells are increased and the damage is heavier. From this, it was revealed that L-norvaline can improve myocardial apoptosis in Myocardial Infarction (MI) mice.
The invention provides a medicine for treating ventricular remodeling after myocardial infarction, and the effective components of the medicine comprise L-norvaline and pharmaceutically acceptable auxiliary materials. As one embodiment, a physiological saline solution of L-norvaline at a desired concentration can be prepared according to actual needs. The administration time and the administration times of the ventricular remodeling drug for treating myocardial infarction of the present invention need to be determined according to the specific diagnosis result of the condition, which is within the technical scope of the person skilled in the art. For example, it will be apparent to one of ordinary skill in the art that a treatment regimen for the reconstruction of the heart chambers of a mouse following myocardial infarction is applied to a human, and that the effective dose of the drug used to the human can be scaled by the effective dose of the drug to the mouse. In a specific embodiment of the present invention, the L-norvaline solution concentration is 7.5mg/mL, and the mice are administered by gastric lavage at a dose of 50 to 80 mg/kg/day.
In the present invention, the auxiliary materials include diluents, buffers, suspensions, emulsions, granules, capsules, excipients, fillers, binders, sprays, transdermal absorbents, wetting agents, disintegrants, absorption promoters, surfactants, colorants, flavoring agents or adsorption carriers.
In the present invention, the dosage forms of the medicine include tablets, powders, granules, capsules, decoctions, oral liquids, injections or suppositories. L-norvaline can be prepared into a proper pharmaceutical preparation according to animal diseases and the application position so as to be convenient for application. In the present invention, as an embodiment, when L-norvaline is prepared into an injection, the pharmaceutically acceptable carrier may be water for injection, sodium chloride, sodium citrate, citric acid, glycerol, ethanol, propylene glycol or the like; the L-norvaline injection can be added with proper additives such as osmotic pressure regulator, pH value regulator, solubilizer, therapeutic oxygen agent, bacteriostat, emulsifier, suspending agent, etc. according to the property of the medicine, wherein the solubilizer is any one or two of polyethylene glycol 400 and tween-80.
The technical solutions of the present invention will be clearly and completely described in the following in connection with the embodiments of the present invention. It will be apparent that the described embodiments are only some, but not all, embodiments of the invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Example 1 mouse Myocardial Infarction (MI) model establishment
Mice were injected intraperitoneally with 4% chloral hydrate (0.01 mL/g) at 10 μl/g mouse body weight, and pressure was applied to the tail end and limbs of the rat tail with forceps, and when the mice had no reflex reaction, the mice were considered to have been fully anesthetized. Fully anesthetized mice were placed on a thermostatic pad at 37 ℃ and were dehaired on their neck and chest, the mice neck was exposed and sterilized with 75% alcohol. The neck skin, muscle and tissue on the trachea are separated and covered along a straight line under a microscope, and when the trachea is exposed, a small hole is cut between two tracheal cartilage rings under the glottis, and a tracheal cannula is inserted for fixation. Examination of the movement of the thorax ensures good ventilation of both lungs (120 breaths/min). Then, a transverse incision is made at the fourth and fifth intercostal positions of the left edge of the sternum of the mice under a microscope by using a pair of scissors, the incision is about 1.2cm long, chest wall muscles are separated layer by layer until intercostal muscles are exposed, intercostal muscles are passively separated by using a pair of forceps, the heart is exposed, and the left anterior descending branch artery (between the left auricle and the pulmonary artery cone, and the left auricle and the pulmonary artery cone are not visible by naked eyes), so that the ligation is successfully carried out under the condition of ischemia (whitening) of the tip of the heart. The intercostal muscles and chest wall muscles are sutured. The intercostal muscles, chest wall muscles and skin were sutured, and the breathing tube was pulled out after the mice were stimulated to respond. The postoperative wound is disinfected by iodine, and if the postoperative wound has the sign of dehydration, sterile physiological salt is timely injected into the abdominal cavity. After the mice wake up, the mice are taken down from the constant temperature pad and put back into the mouse cage;
The procedure of the Sham group operation is identical to the above procedure except that the ligation portion is not performed.
Elimination of the intestinal flora of mice using mixed Antibiotics (ABX)
To exclude the effect of the metabolism of the mice own intestinal flora, we performed antibiotic treatment on mice for one week to eliminate microorganisms in the mice intestinal tract. The specific method comprises the following steps:
Ampicillin AMPICILLIN (0.25 mg/mL), neomycin neomycin (0.25 mg/mL), vancomycin (0.125 mg/mL) and metronidazole metronidazole (0.25 mg/mL) were used in combination, and the prepared reagent was abbreviated as ABX for mice to drink. The drinking water bottle for mice is wrapped by tinfoil and protected from light, and strong light irradiation is avoided. After 3 weeks of myocardial infarction surgery, the antibiotic drinking regimen was performed for 1 week, with 1 water change every 2 days to prevent deterioration of the body.
Example 2L application of norvaline in preparation of medicines for treating ventricular remodeling after myocardial infarction
L-norvaline reagent (Sigma, cat: N7627-10G) was purchased from Sigma and a 7.5mg/mL solution of L-norvaline was prepared with physiological saline. After 1 week of antibiotic treatment in the Myocardial Infarction (MI) mice of example 1, the mice were given a dose of 60mg/kg/day for 8 weeks of gavage. The specific steps of the gastric lavage administration are as follows: left hand mice (25 g/mouse) were held with their heads unrotated and their bodies upright. The mice were dosed with corresponding doses of L-norvaline solution using a 1mL syringe equipped with a 12 gauge gastric lavage flat head needle, based on their body weight. Note that the needle should be gently pressed against the mouse tongue, and the administration should be performed after penetrating the mouse esophagus vertically downward along the tongue without resistance. After the completion of the intragastric administration, the needle was gently withdrawn and the mice were returned to the cage.
Mouse heart ultrasound detection
After 8 weeks of L-norvaline administration, mice were anesthetized with 1.5% -2% isoflurane and then treated with FUJIFILM VisualSonics at a frequency of 30MHz2100 Mice ultrasound imaging system to assess cardiac function in mice. Left ventricular cardiography (major and minor axes) of the B mode was acquired, and M mode cardiography was acquired at the maximum diameter of the left ventricle, and was measured using LV WALL TRACE. The left ventricular Ejection Fraction (EF) and the left ventricular short axis shortening Fraction (FS) were measured. The individual experimental indicators of each mouse were measured 3 times and averaged.
Hematoxylin-eosin (HE) staining of mouse myocardial tissue
The resulting mouse heart tissue samples were fixed in 4% paraformaldehyde solution, and paraffin samples of heart tissue were prepared by dehydration embedding. Paraffin sections were cut to a thickness of 5 μm each. Paraffin sections of the heart tissue of the mice are baked for 2 hours in an oven at 65 ℃ and then put into xylene for dewaxing, then ethanol concentration is gradually reduced for hydration, and then the sections are dyed by adopting an HE dyeing kit (Keygen, cat: KGA 224). The specific dyeing steps are as follows: firstly, 1 drop (50-100 mu L) of hematoxylin dye solution is dripped on a tissue slice for dyeing for 5-10min, and distilled water is used for flushing the dye solution. Then 1 drop (50-100 mu L) of compound dye liquor is dripped for dyeing for 5min, and the dye liquor is flushed. Then one drop (50-100 mu L) of phosphomolybdic acid is dripped for dyeing for 1min, and the product is dried or naturally dried. Finally, a drop (50-100 mu L) of bright green dye liquor is dripped for dyeing for 5min, the dye liquor is washed off, and the mixture is put into an oven for drying at 50-60 ℃ and is sealed by neutral resin. The glass slide is placed under a microscope for observation and photographing, the cytoplasm of the myocardial tissue is red, and the nucleus is purple blue. Images were acquired by NIS-ELements BR software and cardiomyocyte cross-sectional areas were measured using ImageJ software.
Wheat malt lectin (WGA) staining of mouse myocardial tissue
The resulting cross-section samples of mouse heart tissue were placed in OCT complexes and frozen to shape at-80 ℃. Frozen sections of mouse heart tissue were prepared by a frozen microtome and WGA stained with the following specific staining steps: the frozen sections were first rewarmed for 15-30min, washed 3 times with PBS buffer for 5min each. Next, the mixture was fixed with 4% paraformaldehyde for 15min and washed 3 times with PBS buffer for 5min each. Further, WGA-FITC (Sigma, cat: L4895) was used, the dye solution was incubated for 30min under dark conditions, and washed with PBS buffer. Finally, the mixture is incubated for 30min in the dark with Hoechst (Keygen, cat: KGA 212-1) dye solution, washed with PBS buffer solution, and sealed with 50% glycerol under dark conditions. Observed under a fluorescence microscope (CarL Zeiss Microscopy GmbH) (Hoechst excitation wavelength 375nm, corresponding emission wavelength 425nm, indicated by blue light; WGA-FITC excitation wavelength 485nm, emission wavelength 525nm, indicated by green light), images were acquired by ZEN software and myocardial cell cross-sectional areas were measured with imageJ.
Western Blotting (Western Blotting) detection
Firstly, carrying out protein extraction on heart tissue of a mouse: cutting a rice grain size tissue sample from heart tissue of a mouse, placing the tissue sample into a 2mL EP tube containing steel balls and 400 mu L of protein lysate, and vibrating the tissue sample in a tissue crusher for 3min at a frequency of 60 Hz; the steel beads were removed and, after 20min of lysis on ice, centrifuged at 12000rpm for 20min at 4℃and the supernatant was aspirated into a fresh 1.5mL EP tube. Then, concentration measurement and protein determination operation are carried out on the extracted protein: preparing 120 mu L of BSA gradient standard solution in 6 1.5mL EP pipes according to the concentration of 2mg/mL, 1.5mg/mL, 1mg/mL, 0.5mg/mL, 0.25mg/mL and 0mg/mL by using 2mg/mL of BSA standard solution; diluting 10 mu L of the protein stock solution by 10 times; respectively adding a BSA standard solution and a protein solution into the 96-well ELISA plate, wherein each well contains 25 mu L of BSA standard solution 3 and protein solution 2; BCA working fluid is prepared from the following components: solution B = 100:1, preparing, wherein 200 mu LBCA of working solution is added into each hole; after the liquid adding is finished, incubating the 96-well ELISA plate for 30min at 37 ℃; absorbance was measured using a SpectraMax iD3 microplate reader to determine protein concentration; and selecting proper concentration protein according to the concentration of the protein to be measured, adding loading buffer into each tube of protein according to proper proportion, and carrying out metal bath at 100 ℃ for 10min after preparation. And obtaining the prepared protein sample. Electrophoresis and transfer were then performed: preparing SDS-PAGE gel and 1 Xelectrophoresis liquid, and sequentially adding 3 mu L of protein Marker and 7 mu L of protein sample into the sample hole; firstly, electrophoresis is carried out by adopting 80V voltage, and the voltage is regulated to 120V when the strip runs to the separation gel; after electrophoresis, under the condition of 300mA constant current, setting the membrane transferring time according to the molecular weight of the required protein, and transferring the protein onto the PVDF membrane. Finally, incubation of antibody and exposure development: sealing PVDF film in 5% milk powder at room temperature for 2 hr; after the end of the sealing, PBST is washed for 3 times, each time for 5min; adding the primary antibody, and incubating overnight at 4 ℃ on a slow shaking table; recovering primary antibody, and washing with PBST for 3 times, each time for 10min; adding the corresponding secondary antibody, and incubating for 2 hours on a slow shaking table at room temperature; pouring out the secondary antibody, and washing with PBST for 3 times, each time for 10min; exposure and development, acquisition by using a natural energy imaging system and data processing of the pictures by using ImageJ.
Comparative example 1
Unlike example 2, the mice with Myocardial Infarction (MI) of example 1 were given normal saline by gavage, which was unchanged from the procedure.
Analysis of results
A in fig. 1 is a cardiac ultrasound representative graph of a Myocardial Infarction (MI) mouse after administration by gastric lavage with physiological saline; b in FIG. 1 is a representation of cardiac ultrasound after administration of L-norvaline by gastric lavage in Myocardial Infarction (MI) mice. It can be seen that the cardiac function of the L-norvaline group mice was improved compared to the normal saline group mice administered by lavage.
The left ventricular ejection fraction (EF,%) of cardiac ultrasound in the gastric lavage administered L-norvaline mice in fig. 2 was significantly increased compared to the saline group; the fractional shortening of the left ventricular short axis (FS,%) of the heart ultrasound was also significantly elevated compared to the saline group. From FIGS. 1 to 2, it can be seen that L-norvaline can improve cardiac function in Myocardial Infarction (MI) mice.
A in fig. 3 is a cross-sectional representation of the heart of a Myocardial Infarction (MI) mouse following administration by gastric lavage with physiological saline; b in FIG. 3 is a cross-sectional representation of the heart of a Myocardial Infarction (MI) mouse following administration by L-norvaline lavage. The cross-sectional view of myocardial cells detected by H & E staining and the statistical result of the cell size of the myocardial cross section (figure 4) show that the myocardial cells of mice in a normal saline lavage administration group are obviously larger, and the myocardial cells of the mice are obviously reduced after L-norvaline treatment.
The invention also analyzes myocardial tissue of mice in Myocardial Infarction (MI) model by malt lectin (WGA) staining (figures 5-6), results are consistent with H & E staining detection results, myocardial cells of mice in physiological saline lavage administration group are obviously larger, and myocardial cells of the mice are obviously reduced after L-norvaline treatment, which indicates that L-norvaline can improve pathological cardiac hypertrophy of the mice in Myocardial Infarction (MI). From these results, L-norvaline can improve pathological myocardial hypertrophy of Myocardial Infarction (MI) mice.
In the present invention, the L-norvaline reduces myocardial apoptosis caused by myocardial infarction. Apoptosis occurs in close association with Bax/Bcl2 and the expression level of the pair of apoptosis-regulating genes. According to the invention, western immunoblotting (Western Blotting) is used for detecting a Western immunoblotting detection strip chart of Bax and Bcl 2 protein expression conditions in heart tissues of a Myocardial Infarction (MI) mouse respectively after gastric lavage administration of normal saline and L-norvaline; b in FIG. 8 is the statistics of Bax/Bcl 2 protein expression. Studies show that the Myocardial Infarction (MI) model mice have reduced Bax protein expression and Bcl 2 protein expression after 8 weeks of L-norvaline administration, and the Bax/Bcl 2 ratio is reduced, which indicates fewer apoptotic cardiomyocytes and reduced injury. And after the normal saline is used for lavage of mice with a dosing model, the Bax protein expression is obviously increased, the Bcl 2 protein expression is obviously reduced, the Bax/Bcl 2 ratio is obviously increased, and the apoptosis myocardial cells are increased and the damage is heavier. From this, it was revealed that L-norvaline can improve myocardial apoptosis in Myocardial Infarction (MI) mice.
In conclusion, after the treatment of the L-norvaline based mouse model with Myocardial Infarction (MI), the heart function, histological hematoxylin-eosin (HE) staining and malt lectin (WGA) staining are detected by heart ultrasound to detect the size of myocardial cross-section cells, and Western blotting (Western blotting) is used for detecting myocardial apoptosis, so that the L-norvaline can improve heart failure and ventricular remodeling caused by myocardial infarction of the mouse. Accordingly, the L-norvaline can be applied to the preparation of medicaments for treating ventricular remodeling after myocardial infarction.
The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.
Claims (5)
1. An application of L-norvaline in preparing medicines for treating ventricular remodeling after myocardial infarction.
2. The use according to claim 1, wherein the myocardial infarction comprises cardiovascular disease induced myocardial infarction.
3. The use according to claim 1, wherein the L-norvaline improves cardiac dysfunction caused by myocardial infarction.
4. The use according to claim 1, wherein the L-norvaline improves cardiomyocyte hypertrophy caused by myocardial infarction.
5. The use according to claim 1, wherein the L-norvaline reduces myocardial apoptosis caused by myocardial infarction.
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| CN107007605A (en) * | 2017-06-07 | 2017-08-04 | 淮安市第人民医院 | Sanguinarine is preparing the application in suppressing ventricular remodeling after myocardial infarction medicine |
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| CN114306305A (en) * | 2022-02-25 | 2022-04-12 | 上海大学 | Application of protocatechuic acid in preparation of medicine for improving ventricular remodeling and/or heart failure after myocardial infarction |
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| CN107007605A (en) * | 2017-06-07 | 2017-08-04 | 淮安市第人民医院 | Sanguinarine is preparing the application in suppressing ventricular remodeling after myocardial infarction medicine |
| CN111514124A (en) * | 2020-04-13 | 2020-08-11 | 上海大学 | Application of 3-hydroxyphenylacetic acid in preparation of medicine for improving pathologic ventricular remodeling and/or heart failure after myocardial infarction |
| CN114306304A (en) * | 2022-02-25 | 2022-04-12 | 上海大学 | Application of 4-hydroxybenzoic acid in preparing medicine for improving myocardial infarction complication and medicine |
| CN114306305A (en) * | 2022-02-25 | 2022-04-12 | 上海大学 | Application of protocatechuic acid in preparation of medicine for improving ventricular remodeling and/or heart failure after myocardial infarction |
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