CN115350174A - Application of L-norvaline in preparation of medicine for treating ventricular remodeling after myocardial infarction - Google Patents
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- CN115350174A CN115350174A CN202211195776.4A CN202211195776A CN115350174A CN 115350174 A CN115350174 A CN 115350174A CN 202211195776 A CN202211195776 A CN 202211195776A CN 115350174 A CN115350174 A CN 115350174A
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- 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]
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- 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
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- 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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Abstract
The invention provides application of L-norvaline in preparation of a medicine for treating ventricular remodeling after myocardial infarction, and relates to the technical field of biological medicines. The invention discovers that: the 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 firstly defines that the L-norvaline can improve the ventricular remodeling and the heart failure caused by the myocardial infarction, provides a new medicine research and development approach and a medicine action target point for the treatment of the ventricular remodeling and the heart failure caused by the myocardial infarction, and has very important medicinal value.
Description
Technical Field
The invention relates to the technical field of biomedicine, in particular to application of L-norvaline in preparation of a medicine for treating ventricular remodeling after myocardial infarction.
Background
Myocardial Infarction (MI) is Myocardial necrosis caused by acute, persistent ischemic hypoxia of coronary arteries. The myocardial infarction is sudden in onset and high in death rate, and is one of serious diseases seriously harming the life health of human beings. With the development of therapeutic means such as direct coronary intervention (PCI) and thrombolytic therapy, the acute-phase mortality rate of myocardial infarction is greatly reduced, but the subsequent pathological ventricular remodeling and heart failure of patients with myocardial infarction still bring huge burden to the medical security system. Therefore, continuously optimizing the drug treatment scheme and seeking the occurrence mechanism of heart failure caused by myocardial infarction have positive significance for treating cardiovascular diseases.
Intestinal microorganisms play an important regulatory role in human health and development of disease. In recent years, there has been increasing evidence that changes in gut microbiota are associated with a variety of diseases including obesity, type ii diabetes, fatty liver, hypertension, heart failure and myocardial infarction. Our earlier studies found that L-Norvaline (L-Norvaline) is a metabolite in serum that is associated with intestinal microorganisms. In another study, L-norvaline was found to be present at lower levels in intestinal metabolites in breast cancer patients than in healthy subjects, and further studies have shown that L-norvaline can inhibit the proliferative activity of breast cancer cells. It was reported that the faeces of vaginally delivered infants were associated with a high abundance of DL-norvaline which was significantly positively associated with the intestinal probiotic bifidobacteria. Furthermore, L-norvaline is a pharmaceutical intermediate of perindopril, ACE-inhibitors, antihypertensive. However, there have been no studies and inventions related to the treatment of heart failure caused by myocardial infarction with L-norvaline.
Disclosure of Invention
The invention aims to provide application of L-norvaline in preparing a medicament 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 the myocardial infarction and reduce myocardial cell apoptosis caused by the myocardial infarction.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides application of L-norvaline in preparation of 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 cardiomyocyte hypertrophy resulting from myocardial infarction.
Preferably, the L-norvaline reduces apoptosis of myocardial cells caused by myocardial infarction.
The invention provides a medicine for treating ventricular remodeling after myocardial infarction, which comprises the effective components of L-norvaline and pharmaceutically acceptable auxiliary materials.
Preferably, the adjuvant comprises a diluent, a buffer, a suspension, an emulsion, a granule, an encapsulating agent, an excipient, a filler, an adhesive, a spray, a transdermal absorbent, a wetting agent, a disintegrating agent, an absorption enhancer, a surfactant, a coloring agent, a flavoring agent, or an adsorption carrier.
Preferably, the dosage form of the medicine comprises tablets, powder, granules, capsules, decoction, oral liquid, injection or suppository.
Compared with the prior art, the invention has the following effects:
the invention provides application of L-norvaline in preparation of a medicament 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 the myocardial infarction and reduce myocardial cell apoptosis caused by the myocardial infarction. The invention first defines that the L-norvaline can improve the heart failure caused by myocardial infarction, provides a new medicine research and development way and a medicine action target point for the treatment of the heart failure caused by the myocardial infarction and ventricular remodeling, and has very important medicinal value.
Drawings
FIG. 1 is a representative image of cardiac ultrasound after intragastric administration in Myocardial Infarction (MI) mice; wherein, A: and (B) administration by gavage with physiological saline, wherein: l-norvaline is administered by intragastric administration.
FIG. 2 is a graph of the statistics of left ventricular ejection fraction (EF,%) and left ventricular short axis shortening fraction (FS,%) of mouse cardiac ultrasound; wherein denotes p <0.001.
Fig. 3 is a representative image of a hematoxylin-eosin (HE) stained heart cross-section following intragastric administration in Myocardial Infarction (MI) mice, wherein a: and (2) administration by gastric lavage with physiological saline, B: l-norvaline is administered by intragastric administration.
FIG. 4 is a cell size statistic of a hematoxylin-eosin (HE) stained myocardial cross-section; wherein denotes p <0.001.
Fig. 5 is a representation of malt lectin (WGA) stained heart cross-sections following intragastric administration in Myocardial Infarction (MI) mice, wherein a: and (B) administration by gavage with physiological saline, wherein: l-norvaline is administered by intragastric administration.
FIG. 6 is a cell size statistic of malt lectin (WGA) stained myocardial cross-sections; wherein denotes p <0.001.
FIG. 7 shows Bax and Bcl in heart tissue of Myocardial Infarction (MI) mice after gastric administration of physiological saline and L-norvaline, respectively 2 Protein expression profile western blot detection of protein expression.
FIG. 8 shows Bax/Bcl 2 Protein expression statistics; wherein represents p<0.01。
Detailed Description
The invention provides application of L-norvaline in preparation of a medicament for treating ventricular remodeling after myocardial infarction. In the present invention, the source of L-norvaline is not particularly limited. In a specific example of the invention, the L-norvaline reagent was purchased from Sigma, cat: N7627-10G. As an embodiment, a solution of L-norvaline at a desired concentration is prepared using physiological saline.
In the present invention, the myocardial infarction includes myocardial infarction induced by cardiovascular diseases.
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 can lead to ischemic heart failure. The research of the invention shows that: after 8 weeks of L-norvaline administration to Myocardial Infarction (MI) mice by means of gastric lavage, left ventricular Ejection Fraction (EF) and left ventricular short axis shortening Fraction (FS) are determined, and compared with mice administered with normal saline by means of gastric lavage, the left ventricular Ejection Fraction (EF) and the left ventricular short axis shortening Fraction (FS) of the mice treated by the method are remarkably improved, which shows that the cardiac function of the mice can be improved by means of L-norvaline administration.
In the present invention, the L-norvaline improves cardiomyocyte hypertrophy caused by myocardial infarction. The cross sectional area of the myocardial cells is detected by H & E staining, and experimental results show that the myocardial cells of mice in a normal saline intragastric administration group are obviously larger, and the myocardial cells of the mice are obviously reduced after being treated by L-norvaline, which indicates that the L-norvaline can improve the pathological myocardial hypertrophy of Myocardial Infarction (MI) mice. The myocardial tissue of a Myocardial Infarction (MI) model mouse is analyzed by malt agglutinin (WGA) staining, the result is consistent with the H & E staining detection result, the myocardial cells of the mouse in a normal saline intragastric administration group are obviously larger, the myocardial cells of the mouse are obviously reduced after the L-norvaline treatment, and the L-norvaline is shown to be capable of improving the pathological myocardial hypertrophy of the MI model mouse.
In the present invention, the L-norvaline reduces apoptosis of myocardial cells caused by myocardial infarction. Apoptosis and Bax/Bcl 2 The expression levels of the pair of apoptosis-regulating genes are closely related. The results of protein immunoblotting (Western Blotting) detection research show that the Bax protein expression of Myocardial Infarction (MI) model mice is reduced and the Bcl is reduced after the L-norvaline is administrated for 8 weeks 2 Increased protein expression, bax/Bcl 2 The ratio decreased, suggesting fewer apoptotic cardiomyocytes and decreased damage. After the normal saline is used for gastric perfusion administration of the model mouse, the expression of Bax protein is obviously increased, and Bcl is 2 Protein expression is obviously reduced, bax/Bcl 2 The ratio is obviously increased, which indicates that apoptotic myocardial cells are increased and the damage is serious. It was thus demonstrated that L-norvaline can improve myocardial apoptosis in Myocardial Infarction (MI) mice.
The invention provides a medicine for treating ventricular remodeling after myocardial infarction, which comprises the effective components of L-norvaline and pharmaceutically acceptable auxiliary materials. As an embodiment, a solution of L-norvaline at a desired concentration can be prepared using physiological saline according to actual needs. The time and frequency of administration of the drug for ventricular remodeling after myocardial infarction for treatment according to the present invention will depend on the particular diagnosis of the condition, and is within the skill of one skilled in the art. For example, it will be apparent to those skilled in the art that the treatment regimen for ventricular remodeling after myocardial infarction in mice can be applied to humans by converting the effective dose of the drug to the human to the effective dose of the drug to the mouse. In a specific embodiment of the invention, the L-norvaline solution is administered to mice at a concentration of 7.5mg/mL by gavage at a dose of 50-80 mg/kg/day.
In the present invention, the adjuvant includes a diluent, a buffer, a suspension, an emulsion, a granule, a capsule, an excipient, a filler, an adhesive, a spray, a transdermal absorbent, a wetting agent, a disintegrant, an absorption enhancer, a surfactant, a coloring agent, a flavoring agent, or an adsorption carrier.
In the invention, the dosage form of the medicine comprises tablets, powder, granules, capsules, decoction, oral liquid, injection or suppository. The L-norvaline can be prepared into a proper pharmaceutical preparation according to the condition of animals and the application position so as to be convenient to use. In the present invention, as an embodiment, when L-norvaline is prepared as an injection, the pharmaceutically acceptable carrier may be water for injection, sodium chloride, sodium citrate, citric acid, glycerin, ethanol, propylene glycol, etc.; the L-norvaline injection can also be added with appropriate additives according to the properties of the medicine, such as osmotic pressure regulator, pH regulator, solubilizer, therapeutic oxygen agent, bacteriostatic agent, emulsifier, suspending agent, etc., wherein the solubilizer is one or two of polyethylene glycol 400 and tween-80.
The technical solution of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. It is to be understood that the described embodiments are merely exemplary of the invention, and not restrictive of the full scope of the invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1 mouse Myocardial Infarction (MI) model establishment
4% chloral hydrate (0.01 mL/g) is injected into the abdominal cavity of a mouse according to the weight of the mouse of 10 mu L/g, the tail end and the four limbs of the mouse are pressed by tweezers, and the mouse is considered to be fully narcotized when the mouse has no reflex reaction. Fully anesthetized mice were placed on a 37 ℃ constant temperature pad, their necks and breasts were depilated, the necks of the mice were exposed, and the mice were sterilized with 75% alcohol. Separating neck skin, muscle and tissue covered on trachea along straight line under microscope, cutting a small hole between two tracheal cartilage rings under glottis after trachea is exposed, inserting tracheal cannula, and fixing. Examination of the movement of the thorax ensures good ventilation of both lungs (120 breaths/min). Then under a microscope, a transverse incision is made at the fourth, fifth, intercostal position of the left edge of the left sternum of the mouse by using small scissors, the incision is about 1.2cm long, chest wall muscles are separated layer by layer until the intercostal muscles are exposed, the intercostal muscles are separated bluntly by using a pair of microscopic forceps, the heart is exposed, and the left anterior descending artery (between the left auricle and the pulmonary artery cone, the ligation is determined according to the ischemia (whitening) condition of the lower apical part because the ligation is invisible to the naked eye) is ligated. The intercostal muscles and the chest wall muscles are sutured. The intercostal muscles, the muscles of the chest wall and the skin are sutured, and the respiratory tube is pulled out after the stimulation of the mouse has reaction. Iodine tincture sterilization is carried out on the wound after the operation, and if dehydration is shown after the operation, sterile physiological salt is injected into the abdominal cavity in time. Taking down the mouse from the constant temperature pad until the mouse wakes up, and putting the mouse back into the mouse cage;
the Sham (Sham) group of procedures are identical to those described above except that the ligation component is not performed.
Eliminating intestinal flora of mice by using mixed Antibiotics (ABX)
To exclude the effect of the metabolism of the intestinal flora of the mice, the mice were subjected to a one-week antibiotic treatment to eliminate the microorganisms in the intestinal tract of the mice. The specific method comprises the following steps:
the four antibiotics of Ampicillin Ampicillin (0.25 mg/mL), neomycin (0.25 mg/mL), vancomycin (0.125 mg/mL) and metronidazole (0.25 mg/mL) were used in combination, and the prepared reagent is called ABX for mouse drinking. The drinking water bottle for mice needs to be wrapped by tinfoil to avoid light and strong light irradiation. After 3 weeks of myocardial infarction operation, the mice were administered an antibiotic drinking regimen for 1 week with 1 water change every 2 days to prevent water deterioration.
Example 2 application of L-norvaline to treatment of post-myocardial infarction ventricular remodeling
L-norvaline reagent (Sigma, cat: N7627-10G) was purchased from Sigma and prepared as a 7.5mg/mL solution of L-norvaline in physiological saline. After 1 week of antibiotic treatment in Myocardial Infarction (MI) mice of example 1, the mice were gavaged at a dose of 60mg/kg/day for 8 weeks. The specific steps of the intragastric administration are as follows: the left hand held mouse (25 g/mouse) was held with the head fixed and the body upright. According to the weight of the mice, the corresponding dose of L-norvaline solution was administered to the mice using a 1mL syringe equipped with a No. 12 gavage flat-headed needle. It should be noted that the administration should be carried out by lightly pressing the needle against the tongue of the mouse and extending the needle vertically downwards along the tongue into the mouse esophagus without resistance. After the intragastric administration, the needle was gently withdrawn and the mouse was returned to the cage position.
Mouse heart ultrasonic detection
8 weeks after L-norvaline administration, mice were anesthetized with 1.5% -2% isoflurane and then FUJIFILM VisualSonics with a frequency of 30MHz
A 2100 mouse ultrasound imaging system to assess cardiac function in mice. Collecting the left ventricle cardiogram (major axis and minor axis) of B model, and collecting the cardiogram of M model at the maximum diameter of the left ventricle, and measuring by adopting LV wall trace. Left ventricular Ejection Fraction (EF) and left ventricular short axis shortening Fraction (FS) were measured. Each experimental index was measured 3 times per mouse and averaged.
Hematoxylin-eosin (HE) staining of mouse myocardial tissue
The obtained mouse heart tissue sample was fixed in a 4% paraformaldehyde solution, and then a paraffin sample of the heart tissue was prepared by dehydration-embedding. Paraffin sections were cut, each 5 μm thick. Paraffin sections of mouse heart tissues are baked in an oven at 65 ℃ for 2h, then are put into dimethylbenzene for dewaxing, the ethanol concentration is gradually reduced for hydration, and then the sections are dyed by an HE (Heygen, cat: KGA 224) dyeing kit. The specific dyeing steps are as follows: firstly, 1 drop (50-100 mu L) of hematoxylin staining solution is dripped on a tissue slice for staining for 5-10min, and the staining solution is washed away by distilled water. Then 1 drop (50-100 mu L) of composite dye liquor is dripped to dye for 5min, and the dye liquor is washed away. Then, one drop (50-100 mu L) of phosphomolybdic acid is added dropwise for dyeing for 1min, and the solution is dried by spinning or naturally aired. Finally, a drop (50-100 mu L) of brilliant green dye liquor is dripped to dye for 5min, the dye liquor is washed off, and the mixture is put into an oven to be dried at 50-60 ℃ and sealed by neutral gum. The slide glass was observed and photographed under a microscope, and the cytoplasm of the myocardial tissue was red, and the nucleus was purplish blue. Images were collected by NIS-ELements BR software and cardiomyocyte cross-sectional area was measured with ImageJ software.
Wheat Germ Agglutinin (WGA) staining of mouse myocardial tissue
The resulting mouse heart tissue transection samples were placed in OCT complexes and freeze-set at-80 ℃. Frozen sections of mouse heart tissue were prepared by a cryomicrotome and WGA staining was performed, with the specific staining steps: first, the frozen section is rewarmed for 15-30min, and washed 3 times with PBS buffer, 5min each time. Then fixed with 4% paraformaldehyde for 15min, and washed with PBS buffer 3 times for 5min each. WGA-FITC (Sigma, cat: L4895) was added, the resulting dye solution was incubated for 30min in the dark, and washed with PBS buffer. Finally, hoechst (Keygen, cat: KGA 212-1) staining solution is used for incubation for 30min in the dark, and after washing with PBS buffer solution, the cells are sealed with 50% glycerol in the dark. Images were collected by ZEN software and cardiomyocyte cross-sectional area was measured using ImageJ under a fluorescence microscope (CarL Zeiss Microcopy GmbH) (Hoechst excitation wavelength was 375nm, corresponding to an emission wavelength of 425nm, expressed in blue light; WGA-FITC excitation wavelength was 485nm, emission wavelength was 525nm, expressed in green light).
Western Blotting (Western Blotting) assay
First, protein extraction was performed on mouse heart tissue: cutting a tissue sample with the size of rice grains from heart tissue of a mouse, putting the tissue sample into a 2mL EP tube filled with steel balls and 400 mu L of protein lysate, and oscillating for 3min in a tissue crusher according to the frequency of 60 Hz; the steel ball was removed, lysed on ice for 20min, centrifuged at 12000rpm at 4 ℃ for 20min, and the supernatant was pipetted into a fresh 1.5mL EP tube. Then, the concentration determination and protein determination operation are carried out on the extracted protein: using 2mg/mL BSA standard solution to prepare BSA gradient standard solutions at concentrations of 2mg/mL, 1.5mg/mL, 1mg/mL, 0.5mg/mL, 0.25mg/mL, 0mg/mL, 120. Mu.L each in 6 1.5mL EP tubes; diluting 10 μ L of the protein stock solution by 10 times; respectively adding the BSA standard solution and the protein solution into a 96-well enzyme label plate, wherein each well is 25 mu L, the BSA standard solution is repeated for 3, and the protein solution is repeated for 2; BCA working solution according to A: liquid B =100:1, preparing, and adding 200 mu of LBCA working solution into each hole; after the liquid adding, incubating a 96-hole enzyme label plate for 30min at 37 ℃; measuring the light absorption value by using a SpectraMax iD3 enzyme-linked immunosorbent assay to determine the protein concentration; selecting proper concentration protein according to the concentration of the protein to be detected, simultaneously adding loading buffer into each tube of protein according to a proper proportion, and carrying out metal bath for 10min at 100 ℃ after the preparation is finished. And obtaining a prepared protein sample. Then, electrophoresis and membrane transfer are carried out: preparing SDS-PAGE gel and 1 × electrophoresis liquid, and sequentially adding 3 μ L of protein Marker and 7 μ L of protein sample into the sample hole; firstly, carrying out electrophoresis by adopting 80V voltage, and adjusting the voltage to 120V when the strip runs to the separation gel; after electrophoresis is finished, under the condition of a constant current of 300mA, the membrane transferring time is set according to the molecular weight of the needed protein, and the protein is transferred to the PVDF membrane. Finally, antibody incubation and exposure development: sealing the PVDF membrane in 5% milk powder at room temperature in a slow shaking table for 2 hours; after the sealing is finished, PBST is washed for 3 times, and each time lasts for 5min; adding primary antibody, and incubating overnight at 4 deg.C on a slow shaker; recovering primary antibody, and washing with PBST for 3 times, each for 10min; adding corresponding secondary antibody, and incubating for 2h at room temperature on a slow shaking table; the secondary antibody is poured off, and PBST is washed for 3 times, 10min each time; and (4) exposure and development, wherein the images are collected by using a solar imaging system and are subjected to data processing by using ImageJ.
Comparative example 1
In contrast to example 2, the Myocardial Infarction (MI) mice of example 1 were gavaged with normal saline, which was not changed from the procedure.
Analysis of results
A in FIG. 1 is a representative diagram of cardiac ultrasound after gastric administration of a normal saline solution to a Myocardial Infarction (MI) mouse; b in FIG. 1 is a representation of cardiac ultrasound following gastric administration of L-norvaline in Myocardial Infarction (MI) mice. It can be seen that the cardiac function of the mice of the L-norvaline group was improved as compared with the mice of the group administered with physiological saline by gavage.
In FIG. 2, the left ventricular ejection fraction (EF,%) of the cardiac ultrasound of the mice administered with L-norvaline by gavage is significantly increased compared with that of the normal saline group; the left ventricular short axis fractional shortening (FS,%) of the mouse cardiac ultrasound was also significantly increased compared to the saline group. It can be seen from FIGS. 1 to 2 that L-norvaline can improve cardiac function in Myocardial Infarction (MI) mice.
FIG. 3A is a cross-sectional representation of the heart of a Myocardial Infarction (MI) mouse following gastric administration by saline gavage; b in FIG. 3 is a representation of a cross-sectional view of the heart after gastric administration of L-norvaline in Myocardial Infarction (MI) mice. The H & E staining detection of the cross section image of the myocardial cells and the cell size statistical result (figure 4) of the myocardial cross section show that the myocardial cells of mice in the group of normal saline intragastric administration are obviously larger, and the myocardial cells of the mice treated by L-norvaline are obviously reduced.
The myocardial tissues of mice of the Myocardial Infarction (MI) model are analyzed by malt agglutinin (WGA) staining (figures 5-6), the result is consistent with the H & E staining detection result, the myocardial cells of the mice in the group administered by normal saline intragastric administration are obviously larger, the myocardial cells of the mice treated by L-norvaline are obviously reduced, and the L-norvaline is shown to be capable of improving the pathological myocardial hypertrophy of the mice with Myocardial Infarction (MI). It was thus found that L-norvaline was able to improve the pathological myocardial hypertrophy in mice with Myocardial Infarction (MI).
In the present invention, the L-norvaline reduces apoptosis of myocardial cells caused by myocardial infarction. The occurrence of apoptosis is closely related to the expression level of Bax/Bcl2 and the apoptosis regulating gene. The invention detects the Ba in the heart tissue of a Myocardial Infarction (MI) mouse after gastric lavage by physiological saline and L-norvaline respectively through Western immunoblotting (Western Blotting) in figure 7x and Bcl 2 Protein immunoblot detection of protein expression profiles; b in FIG. 8 is Bax/Bcl 2 Statistics of protein expression. Studies have shown that Bax protein expression is reduced and Bcl is reduced in Myocardial Infarction (MI) model mice after 8 weeks of L-norvaline administration 2 Increased protein expression, bax/Bcl 2 The ratio decreased, suggesting fewer apoptotic cardiomyocytes and decreased damage. After the gastric administration of the normal saline solution to the model mouse, the Bax protein expression is obviously increased, and the Bcl is 2 Protein expression is significantly reduced, bax/Bcl 2 The ratio is obviously increased, which indicates that apoptotic myocardial cells are increased and the damage is serious. It was thus demonstrated that L-norvaline can improve myocardial apoptosis in Myocardial Infarction (MI) mice.
In conclusion, after the mouse model based on Myocardial Infarction (MI) is treated by the L-norvaline, the cardiac function is detected by cardiac ultrasonic, the sizes of myocardial cross-section cells are detected by histological hematoxylin-eosin (HE) staining and malt agglutinin (WGA) staining, and the myocardial apoptosis condition is detected by protein immunoblotting, so that the L-norvaline is found to be capable of improving the heart failure and ventricular remodeling caused by the mouse myocardial infarction. Therefore, the L-norvaline can be applied to preparing the medicine for treating ventricular remodeling after myocardial infarction.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and amendments can be made without departing from the principle of the present invention, and these modifications and amendments should also be considered as the protection scope of the present invention.
Claims (8)
1. An application of L-norvaline in preparing a medicament for treating ventricular remodeling after myocardial infarction.
2. The use of claim 1, wherein the myocardial infarction comprises a cardiovascular disease-induced myocardial infarction.
3. The use of claim 1, wherein L-norvaline ameliorates cardiac dysfunction due to myocardial infarction.
4. The use of claim 1, wherein L-norvaline ameliorates cardiomyocyte hypertrophy resulting from myocardial infarction.
5. The use of claim 1, wherein the L-norvaline reduces apoptosis of cardiomyocytes caused by myocardial infarction.
6. The medicine for treating ventricular remodeling after myocardial infarction is characterized in that the effective component of the medicine comprises L-norvaline and pharmaceutically acceptable auxiliary materials.
7. The medicament of claim 6, wherein the excipient comprises a diluent, a buffer, a suspension, an emulsion, a granule, an encapsulating agent, an excipient, a filler, an adhesive, a spray, a transdermal absorbent, a wetting agent, a disintegrant, an absorption enhancer, a surfactant, a colorant, a flavoring agent, or an adsorbent carrier.
8. The medicament as claimed in claim 6 or 7, wherein the dosage form of the medicament comprises tablets, powders, granules, capsules, decoctions, oral liquid, injection or suppositories.
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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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| 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 |
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