Application of recombinant echinococcus granulosus secreted antigen B8 / 2 in acute myocardial infarction

Abstract

The invention discloses application of a recombinant echinococcus granulosus secreted antigen B8 / 2 in acute myocardial infarction, and belongs to the technical field of medicinal chemistry. The invention provides a medicine capable of preventing, relieving and / or treating acute myocardial infarction, and the effective component of the medicine is recombinant echinococcus granulosus secreted antigen B8 / 2, which is called rEgAgB8 / 2 for short. The rEgAgB8 / 2 can effectively delay acute myocardial infarction and mouse inflammatory response, reduce the myocardial infarction area, improve cardiac function deterioration and reverse visceral organ pathological damage, and a new thought is provided for clinical treatment of acute myocardial infarction.

Description

Technical Field

[0001] The invention relates to application of recombinant Echinococcus granulosus secretory antigen B8 / 2 in acute myocardial infarction, belonging to the technical field of pharmaceutical chemistry. Background Art

[0002] Myocardial infraction (MI) is the leading cause of death worldwide and is characterized by myocardial ischemia and hypoxia due to arterial obstruction. In China, cardiovascular diseases, including MI, are the leading cause of death among residents, and more than 40% of deaths can be attributed to these diseases. In recent years, more and more studies have shown that the occurrence and development of MI is accompanied by inflammatory responses, and dying cardiomyocytes release damage-associated molecular patterns (DAMPs) to activate the innate immune system. Neutrophils, as the most sensitive sentinels, are first recruited to the infarct site to remove damaged cell debris and initiate the repair process. Subsequently, monocytes are recruited to the inflammatory area and differentiate into different macrophage subsets, among which M1 macrophages promote inflammation in the acute phase, while M2 macrophages contribute to tissue repair and inflammation relief in the recovery phase. Persistent or excessive inflammation can lead to aggravated fibrosis, thereby impairing cardiac function and increasing the risk of heart failure. Therefore, reducing the inflammatory response in the acute phase and regulating the balance between M1 and M2 macrophages are crucial to reducing the mortality rate and improving the prognosis of MI.

[0003] In recent years, many studies have found that parasitic infections can suppress Th1-dominated inflammatory responses in the host by secreting some biologically functional molecules, and induce M2 macrophage polarization to regulate the host immune response, as a survival strategy to reduce the host's immune attack. This immunomodulatory function can be used to treat certain autoimmune or inflammatory diseases. Echinococcus granulosus infects humans or livestock in the larval stage, causing cystic echinococcosis (CE), a widely distributed global zoonosis. Echinococcus granulosus secretory antigen B (EgAgB) is the main protein secreted in its cyst fluid. Due to its high antigenicity, EgAgB has been widely used in the immunodiagnosis of cystic echinococcosis (CE). EgAgB is a polylipoprotein with a molecular weight of approximately 160 kDa, composed of multiple 8 kDa subunits, including five subunits: EgAgB8 / 1, EgAgB8 / 2, EgAgB8 / 3, EgAgB8 / 4, and EgAgB8 / 5. Among them, the recombinant EgAgB8 / 2 protein (GenBank: ACZ51457) showed higher diagnostic value than other recombinant EgAgB subunits and was used for serological diagnosis of human CE. It can also inhibit the production of proinflammatory cytokines by interacting with host immune cells, exert immunomodulatory effects, and thus reduce the host's inflammatory response. Experiments have confirmed that rEgAgB8 / 2 can reduce intestinal inflammation by regulating the polarization of M1 / 2 macrophages. Our previous studies also showed that the secretory / excretory proteins of adult Trichinella spiralis improve mouse MI by regulating the differentiation of macrophages to the M2 type. However, the therapeutic effect of rEgAgB8 / 2 on cardiovascular diseases, especially MI, has not been studied. Summary of the invention

[0004] The purpose of the present invention is to provide the application of rEgAgB8 / 2 in acute myocardial infarction. Animal experiments have confirmed that rEgAgB8 / 2 can delay acute myocardial infarction and inflammatory response in mice, reduce the area of ​​myocardial infarction, improve the deterioration of cardiac function and reverse pathological damage to organs, providing a new idea for the clinical treatment of acute myocardial infarction and its subsequent ventricular remodeling.

[0005] The present invention provides the use of recombinant Echinococcus granulosus secretory antigen B8 / 2 in the preparation of a medicine for preventing, alleviating and / or treating acute myocardial infarction.

[0006] In one embodiment, the amino acid sequence of rEgAgB8 / 2 is as shown in SEQ ID NO.1.

[0007] In one embodiment, the prevention, alleviation and / or treatment of acute myocardial infarction includes at least one of the following:

[0008] (1) Reduce the mortality rate of acute myocardial infarction;

[0009] (2) Reduce heart-to-body weight ratio;

[0010] (3) reduce the size of myocardial infarction;

[0011] (4) Reduce the degree of myocardial fibrosis after myocardial infarction;

[0012] (5) Delaying the damage of cardiac function;

[0013] (6) Inhibit the levels of pro-inflammatory cytokines and increase the expression of immune regulatory factors.

[0014] In one embodiment, the rEgAgB8 / 2 is used alone as an active ingredient of the drug.

[0015] In one embodiment, the effective dose of rEgAgB8 / 2 is 0.25 to 0.5 mg / kg.

[0016] In one embodiment, the application includes mixing the recombinant Echinococcus granulosus secretory antigen B8 / 2 with pharmaceutical excipients to prepare a drug for preventing, relieving and / or treating acute myocardial infarction.

[0017] In one embodiment, the pharmaceutical excipients include fillers, binders, wetting agents, disintegrants, lubricants and / or flavoring agents.

[0018] In one embodiment, the filler is starch, sucrose, lactose, calcium sulfate and / or microcrystalline cellulose; the binder is a cellulose derivative, alginate, gelatin and / or polyvinyl pyrrolidone; the wetting agent is water, ethanol, starch and / or syrup; the disintegrant is sodium carboxymethyl starch, carboxypropyl cellulose, cross-linked carboxymethyl cellulose, agar, calcium carbonate and / or sodium bicarbonate; the lubricant is talc, calcium stearate, magnesium stearate, micropowder silica gel and / or polyethylene glycol; the flavoring agent is monosyrup, sucrose, lecithin, orange peel syrup, cherry syrup, lemon, fennel, peppermint oil, sodium alginate, gum arabic, gelatin, methylcellulose, sodium carboxymethyl cellulose, citric acid, tartaric acid and / or sodium bicarbonate.

[0019] In one embodiment, the drug further contains a pharmaceutically acceptable drug carrier.

[0020] In one embodiment, the drug carrier comprises microcapsules, microspheres, nanoparticles and / or liposomes.

[0021] In one embodiment, the administration route of the drug includes intradermal injection, subcutaneous injection, intravenous injection, intramuscular injection, intraperitoneal injection, intravenous drip, arterial injection, intracavitary injection and / or oral administration.

[0022] In one embodiment, the drug is in the form of powder, granules, capsules, tablets, pills or oral liquid.

[0023] In one embodiment, the drug may further include other active ingredients with similar pharmacological activities.

[0024] Beneficial effects:

[0025] The present invention confirms the preventive and therapeutic effect of rEgAgB8 / 2 on acute myocardial infarction in mice, and provides a new strategy for the prevention and treatment of other common metabolic or immune-related diseases, specifically including:

[0026] (1) Reduce the mortality rate of acute myocardial infarction and reduce heart weight;

[0027] (2) Reduce the size of myocardial infarction;

[0028] (3) Reduce the degree of myocardial fibrosis after myocardial infarction;

[0029] (4) Delaying cardiac function damage;

[0030] (5) Inhibit the levels of pro-inflammatory cytokines and increase the expression of immune regulatory factors.

[0031] The present invention provides a new immunotherapy idea for the treatment of myocardial infarction, which breaks through the limitations of existing treatment strategies. For clinical applications, it may become an auxiliary or alternative treatment method in addition to traditional drug therapy, reducing heart failure and long-term complications after myocardial infarction. It provides a feasible innovative method for the prevention and treatment of cardiovascular diseases, with important social and economic benefits. The present invention demonstrates the potential positive role of parasites in regulating the host immune system, breaking the traditional concept that parasites are only harmful to the host. This helps to further understand the complex relationship between parasites and hosts, expand the treatment field of "worm therapy" (cardiovascular diseases), further improve the molecular mechanism of worm immunomodulatory effects, and provide a new direction for immunotherapy research on human health. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 This is the electrophoresis diagram of purified rEgAgB8 / 2.

[0033] Figure 2 The figure shows the changes in the survival rate of mice in each group 28 days after modeling; (n=18 / group, **P<0.01 vs MI+PBS group).

[0034] Figure 3 The changes in cardiac function of mice in each group 7 days after modeling; A: Typical echocardiogram; B: Changes in heart rate and contractile function indicators of mice in each group when acquiring images; (n=5 / group, *P<0.05, **P<0.01, ***P<0.001vs MI+PBS group).

[0035] Figure 4 The changes in heart-to-body weight ratio of each group of mice 7 days after modeling; (n=6 / group, **P<0.01, ***P<0.001 vs MI+PBS group).

[0036] Figure 5 This is the myocardial infarction area of ​​each group of mice 7 days after model establishment.

[0037] Figure 6 The changes in cardiac structure and fibrosis in each group of mice 7 days after modeling; A: Typical results of HE staining of mice in each group; B: Representative images of Masson staining of coronary sections of the heart (Scale bar: 1000μm; enlarged views of infarct zone, Scale bar: 250μm); (n=5 / group, **P<0.01, ***P<0.001vs MI+PBS group).

[0038] Figure 7 The changes of inflammatory factors and immunomodulatory factors in each group of mice 7 days after modeling; (n=5-6 / group, ***P<0.001vs MI+PBS group). DETAILED DESCRIPTION

[0039] Example 1 Preparation and Purification of rEgAgB8 / 2

[0040] (Nanjing Zhongding Biotechnology Co., Ltd.): A full-length splicing primer was designed based on the PAS (PCR-based Accurate Synthesis) method, and protective base synthetic genes were designed at both ends of the primer. An 8×His tag was added to the C-terminus and the fragment (shown in SEQ ID NO.2) was cloned into the E. coli expression vector pET-28a(+) by homologous recombination. The correct sequence and reading frame of the recombinant EgAgB8 / 2 / pPET-28a(+) were confirmed by double-stranded DNA sequencing. The recombinant plasmid was transformed into E. coli BL21(DE3), cultured at 37°C until it reached the logarithmic phase, and then induced for expression with 1mM IPTG at 30°C for 4 hours. The expressed rEgAgB8 / 2 was a soluble protein and was purified using nickel affinity chromatography. Endotoxins in the purified protein were removed using the ToxOut Endotoxin Removal Kit, and the residual endotoxin level was determined using the ToxinSensor Colorimetric LAL Endotoxin Detection Kit. The purified rEgAgB8 / 2 was stored in PBS buffer without imidazole, and its concentration was determined by BCA protein concentration assay kit. SDS-PAGE was used to confirm the expression and purity of the target protein ( Figure 1 ). The purified rEgAgB8 / 2 was then stored at -80°C for later use.

[0041] Example 2 Effect of rEgAgB8 / 2 on the survival rate of mice with acute myocardial infarction

[0042] (1) Experimental materials:

[0043] Animals: Male C57BL / 6J mice, 6-8 weeks old, SPF grade, weighing approximately 18-22 g, were purchased from the Experimental Animal Center of Bengbu Medical University. All mice were housed in a temperature- and humidity-controlled animal room with a 12-h light / dark cycle and free access to standard rodent chow and water. The room temperature was maintained at 22-24°C and the humidity was controlled at 40-60%. All experimental procedures were performed in accordance with the operating guidelines approved by the Ethics Committee of Bengbu Medical College, with approval number

[2024] 617. Mice were randomly divided into groups using a random number table method, and all analyses were performed under blind conditions, and the experimenters were unaware of the allocation of the groups.

[0044] Apparatus: Reward small animal inhalation anesthesia machine.

[0045] Reagent: Isoflurane.

[0046] (2) Experimental methods:

[0047] The "Erhe Gao MI modeling method" (Erhe Gao, et al. Circ Res, 2010) was used: after anesthesia and disinfection with the gas anesthetic isoflurane, the mice were fixed in the supine position, an oblique incision was made at the 3rd-4th intercostal space of the left chest wall, the muscle tissue of the chest wall was bluntly separated, the chest was squeezed with the left hand, and the heart was gently squeezed at the 4th intercostal space with the right hand to be placed outside the chest cavity, and the left anterior descending branch of the coronary artery was ligated (position: the point where the upper edge of the left atrium and the main vein are equally divided). When the apex of the heart turns gray, the heart is quickly reset, the chest cavity is squeezed to exhaust air, and the incision is sutured to close. The electrocardiogram shows that the myocardium has ischemic manifestations, which proves that the modeling is successful. The acute myocardial infarction period of mice after modeling is 0-7 days.

[0048] The day of modeling was designated as day 0. The experiment was divided into 4 groups, with 18 mice in each group, namely: ① Negative control group (Sham+PBS group): no modeling was performed, and PBS was injected intraperitoneally only on days 1, 3, and 5; ② rEgAgB8 / 2 control group (Sham+rEgAgB8 / 2): no modeling was performed, and rEgAgB8 / 2 (5 μg / mouse) was injected intraperitoneally only on days 1, 3, and 5; ③ MI model group (MI+PBS): PBS was injected intraperitoneally on days 1, 3, and 5 after modeling; ④ MI treatment group (MI+rEgAgB8 / 2): rEgAgB8 / 2 (5 μg / mouse) was injected intraperitoneally on days 1, 3, and 5 after modeling.

[0049] The survival rate of mice in each group was observed and recorded 28 days after model establishment.

[0050] (3) Experimental results:

[0051] The survival status of mice in each group was observed for 28 days, and the results showed that there was no significant difference in the survival rate between the Sham+PBS group and the Sham+rEgAgB8 / 2 group. Within 28 days after MI surgery, the survival rate of mice in the MI+PBS group was 66.7%, which was significantly lower than that of the Sham+PBS group (100%); the survival rate of mice in the MI+rEgAgB8 / 2 group was 94.4%, which was significantly higher than that of the MI+PBS group. The above results show that rEgAgB8 / 2 protein can significantly improve the survival rate of mice after MI surgery ( Figure 2 ), and rEgAgB8 / 2 is safe and nontoxic to mice.

[0052] Example 3 Effect of rEgAgB8 / 2 on cardiac function in mice with acute myocardial infarction

[0053] (1) Experimental materials:

[0054] Animals: Same as Example 2.

[0055] Instruments: Reward small animal inhalation anesthesia machine, small animal ultrasound imaging system (VisualSonics, Canada).

[0056] Reagent: Isoflurane.

[0057] (2) Experimental methods: Ultrasound was performed 7 days after modeling. Five mice were selected from each group. The mice were anesthetized with isoflurane and fixed on the ultrasound operating table. The hair on the left chest was removed with depilatory cream and ultrasound coupling agent was applied. Under stable anesthesia, the mouse cardiac ultrasound examination was performed. The LV trace method was used in the long-axis B Mode to analyze the stroke volume (SV), left ventricular ejection fraction (LVEF), and left ventricular fractional shortening (LVFS) to evaluate the left ventricular systolic function.

[0058] (3) Experimental results:

[0059] Compared with the mice in the Sham+PBS group, the heart morphology of the mice in the Sham+rEgAgB8 / 2 group did not change significantly; the heart cavity of the mice in the MI+PBS group became significantly larger and rounder, with a pear-shaped or spherical shape, and the activity of the anterior and posterior walls of the left ventricle decreased significantly; compared with the MI+PBS group, the heart cavity of the mice in the MI+rEgAgB8 / 2 group became smaller, and the heart cavity morphology and ventricular wall motion were significantly improved ( Figure 3 ).

[0060] Statistical results showed that compared with the Sham+PBS group, there was no significant difference in cardiac function in the Sham+rEgAgB8 / 2 group. The SV, LVEF and LVFS of the MI+PBS group mice decreased significantly 7 days after MI, that is, the left ventricular systolic function decreased significantly. Compared with the MI+PBS group, the SV, LVEF and LVFS of the MI+rEgAgB8 / 2 group mice increased significantly 7 days after MI, that is, the left ventricular systolic function was significantly improved. The above results show that rEgAgB8 / 2 can significantly improve the cardiac dysfunction caused by acute myocardial infarction in MI mice.

[0061] Table 1 Cardiac function of mice in each group

[0062]

[0063] Example 4 Effect of rEgAgB8 / 2 on the heart-to-body weight ratio in mice with acute myocardial infarction

[0064] (1) Experimental materials:

[0065] Sample: Mouse heart collected after killing the mice in Example 3.

[0066] Instrument: Micro electronic balance.

[0067] Reagents: PBS.

[0068] (2) Experimental methods:

[0069] After the ultrasonic imaging measurement in Example 3, the weight of mice in each group was weighed and recorded, and the mouse chest cavity was opened after blood was taken from the eyeball, and the heart was perfused with PBS through the aorta to remove blood. The heart was removed (excess tissue was cut off, and the left and right atrial appendages were retained), washed with PBS again, and dried with filter paper. The heart weight was weighed with a micro electronic scale to calculate the heart to body weight ratio.

[0070] (3) Experimental results:

[0071] Compared with the mice in the Sham+PBS group, rEgAgB8 / 2 did not cause a significant change in the heart-to-body weight ratio of mice, while the heart-to-body weight ratio of mice in the MI+PBS group increased significantly after surgery; after rEgAgB8 / 2 treatment, the heart-to-body weight ratio of mice decreased significantly, which was statistically significant ( Figure 4 ). Calculation method of heart-to-body weight ratio: heart-to-body weight ratio = heart weight (g) / body weight (g).

[0072] The above results indicate that rEgAgB8 / 2 can reduce the heart-to-body weight ratio in mice with acute myocardial infarction.

[0073] Table 2 Heart to body weight ratio of mice in each group

[0074]

[0075] Example 5 Effect of rEgAgB8 / 2 on the Infarct Area of ​​Myocardial Infarction Mice

[0076] (1) Experimental materials:

[0077] Sample: Mouse heart tissue collected in Example 3.

[0078] Instrument: Stereo microscope.

[0079] Reagents: TTC solution.

[0080] (2) Experimental methods:

[0081] After the mouse heart was collected, it was first rinsed with saline and then quickly frozen at -20°C for 10-15 minutes. Subsequently, each heart was cut into 5 slices from the ligation point to the apex, each with a thickness of 1-2 mm. The heart slices were incubated in 1% TTC staining solution at 37°C in the dark for 10-20 minutes. The white area represents infarcted tissue, while the red area represents non-infarcted tissue. The heart morphology was observed and recorded under a microscope, and the infarct area was analyzed by ImageJ software.

[0082] (3) Experimental results:

[0083] Compared with the mice in the Sham+PBS group, rEgAgB8 / 2 did not cause significant changes in the infarct area of ​​the mice's hearts, but after MI modeling, the infarct area increased significantly; compared with the MI+PBS group, the hearts of the mice in the MI+rEgAgB8 / 2 group became smaller and the infarct area decreased. This indicates that rEgAgB8 / 2 has a positive effect on the heart morphology of mice with acute myocardial infarction ( Figure 5 ).

[0084] Table 3 Myocardial infarction area in mice

[0085]

[0086] Example 6 Effect of rEgAgB8 / 2 on cardiac structure and myocardial fibrosis in mice after myocardial infarction

[0087] (1) Experimental materials:

[0088] Sample: Mouse heart tissue collected in Example 3.

[0089] Instrument: Microscope (Nikon, Japan).

[0090] Reagents: xylene, anhydrous ethanol, 75% alcohol, glacial acetic acid, paraffin, Masson staining kit (Servicebio, China), Oil Red O dye, Hematoxylin & Eosin dye (HE) (Servicebio, China).

[0091] (2) Experimental methods:

[0092] The collected heart tissues were washed with pre-cooled PBS and then fixed by immersion in 4% paraformaldehyde, embedded in paraffin and sliced. After dewaxing and hydration, they were stained with hematoxylin and eosin staining solution and Masson staining kit. The slices were read and images were collected under a microscope. The left ventricular wall thickness (LV Wall thickness) and the percentage of fibrosis area (Fibrosis) in the infarcted area were determined using Image J system software.

[0093] (3) Experimental results:

[0094] As time passed after MI surgery, the thickness of the wall of the left ventricle infarct zone of mice showed a downward trend, while the area of ​​fibrosis showed an upward trend. Specifically, compared with the MI+PBS group, the wall of the left ventricle infarct zone of mice in the MI+rEgAgB8 / 2 group was significantly thickened; the area of ​​left ventricular fibrosis was significantly improved, and there was no significant difference between the Sham+PBS group and the Sham+rEgAgB8 / 2 group ( Figure 6 ).

[0095] The above results indicate that rEgAgB8 / 2 can delay the thinning of the left ventricular infarct wall in MI mice, reduce the degree of left ventricular fibrosis, and protect ventricular compliance after MI.

[0096] Table 4 Heart structure and myocardial fibrosis in mice

[0097]

[0098] Example 7 Effect of rEgAgB8 / 2 on the levels of proinflammatory cytokines and immunoregulatory cytokines in mice

[0099] (1) Experimental materials:

[0100] Samples: Mouse serum and heart tissue collected in Example 3.

[0101] Materials: Tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10) ELISA kits (Shanghai Dakoway); reverse transcription kit (TransGen Biotech, China), fluorescence quantitative kit (TransGen Biotech, China)

[0102] Instrument: Roche 96 real-time PCR system (USA).

[0103] (2) Experimental methods:

[0104] After blood was collected from the mouse eyeball, it was centrifuged at 4°C, 4500rpm for 15 minutes, and the mouse serum was collected and stored at -80°C for subsequent ELISA testing. The removed mouse heart tissue was rinsed with pre-cooled PBS, and an appropriate amount of tissue was weighed, added to Trizol lysis buffer, and ground in a homogenizer at 65Hz, 60s, and the total RNA of the heart tissue was extracted according to the steps. Then, a reverse transcription kit was used to synthesize cDNA from 2μg of total RNA. A fluorescent quantitative kit was used, with 2μl cDNA as a template, a total volume of 20μl loading, GAPDH as an internal reference, and the total RNA was extracted at 4 °C. On analysis. -△△Cq , the relative mRNA expression levels of the above cytokines in cardiac tissue were detected.

[0105] (3) Experimental results:

[0106] ELISA kits were used to detect the secretion levels of serum inflammatory factors (TNF-α, IL-10) in each group of mice. PT-PCR technology was used to detect the mRNA expression levels of corresponding inflammatory cytokines in the myocardial infarction area of ​​each group of mice at different time periods (the apical area was detected in the Sham+PBS group and the Sham+rEgAgB8 / 2 group).

[0107] The results show that Figure 7 ), compared with the Sham+PBS group, the level of serum proinflammatory cytokine TNF-α in mice in the MI+PBS group was increased, and compared with the MI+PBS group, the level of serum proinflammatory factor TNF-α in mice in the MI+rEgAgB8 / 2 group was significantly decreased, and the immunoregulatory cytokine IL-10 was significantly upregulated. The mRNA expression levels of proinflammatory factor TNF-α and immunoregulatory factor IL-10 in cardiac tissue were consistent with those in serum. The above results show that rEgAgB8 / 2 treatment can significantly inhibit the expression of proinflammatory factors and promote the expression of immunoregulatory cytokines, thereby protecting myocardial tissue from inflammatory attack.

[0108] Table 5 Secretion levels of inflammatory factors (TNF-α, IL-10) in mouse serum

[0109]

[0110] Although the present invention has been disclosed as above in the form of a preferred embodiment, it is not intended to limit the present invention. Anyone familiar with this technology can make various changes and modifications without departing from the spirit and scope of the present invention. Therefore, the scope of protection of the present invention should be based on the definition of the claims.

Claims

1. Use of antigen B8 / 2 in the preparation of a drug for preventing, alleviating and / or treating acute myocardial infarction, characterized in that: The amino acid sequence of the antigen B8 / 2 is shown in SEQ ID NO.

1.

2. The use according to claim 1, characterized in that: The prevention, relief and / or treatment of acute myocardial infarction includes at least one of the following: (1) Reduce the mortality rate of acute myocardial infarction; (2) Reduce heart-to-body weight ratio; (3) reduce the size of myocardial infarction; (4) Reduce the degree of myocardial fibrosis after myocardial infarction; (5) Delaying the damage of cardiac function; (6) Inhibit the levels of pro-inflammatory cytokines and increase the expression of immune regulatory factors.

3. The use according to claim 1 or 2, characterized in that: The rEgAgB8 / 2 is used alone as an active ingredient of the drug.

4. The use according to claim 1 or 2, characterized in that: The application includes mixing rEgAgB8 / 2 with pharmaceutical excipients to prepare a drug for preventing, alleviating and / or treating acute myocardial infarction and subsequent ventricular remodeling.

5. The use according to claim 4, characterized in that: The pharmaceutical excipients include fillers, binders, wetting agents, disintegrants, lubricants and / or flavoring agents.

6. The use according to claim 5, characterized in that: The filler is starch, sucrose, lactose, calcium sulfate and / or microcrystalline cellulose; the binder is cellulose derivatives, alginate, gelatin and / or polyvinyl pyrrolidone; the wetting agent is water, ethanol, starch and / or syrup; the disintegrant is sodium carboxymethyl starch, carboxypropyl cellulose, cross-linked carboxymethyl cellulose, agar, calcium carbonate and / or sodium bicarbonate; the lubricant is talc, calcium stearate, magnesium stearate, micro powder silica gel and / or polyethylene glycol; the flavoring agent is monosyrup, sucrose, lecithin, orange peel syrup, cherry syrup, lemon, fennel, mint oil, sodium alginate, gum arabic, gelatin, methylcellulose, sodium carboxymethyl cellulose, citric acid, tartaric acid and / or sodium bicarbonate.

7. The use according to claim 1 or 2, characterized in that: The drug also contains a pharmaceutically acceptable drug carrier.

8. The use according to claim 7, characterized in that: The drug carrier comprises microcapsules, microspheres, nanoparticles and / or liposomes.

9. The use according to any one of claims 1 to 8, characterized in that: The dosage form of the medicine is powder, granule, capsule, tablet, pill or oral solution.

10. The use according to any one of claims 1 to 8, characterized in that: The drug may also include other active ingredients with similar pharmacological activities.

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