CN114469940B - Application of small molecule compound AQ-390 in preparing medicine and inhibitor for resisting cell apoptosis - Google Patents

Abstract

The invention discloses an application of a small molecular compound AQ-390 in preparing drugs and inhibitors for resisting cell apoptosis, which comprises the application of the small molecular compound in preparing drugs for resisting cell apoptosis and playing an anti-inflammatory effect to prevent or treat ischemia reperfusion injury by directly inhibiting the activity of GSDMD protein, wherein the drugs can be prepared by taking AQ-390 as an active ingredient and adding pharmaceutically conventional auxiliary agents.

Description

Application of small molecule compound AQ-390 in preparation of drugs and inhibitors for resisting cell apoptosis

Technical Field

The invention relates to the field of chemical biology, in particular to application of a small molecular compound AQ-390 in preparing a medicine for resisting cell apoptosis and playing an anti-inflammatory effect so as to prevent or treat ischemia-reperfusion injury, and also discloses a GSDMD inhibitor prepared based on the medicine.

Background

Currently, the closest prior art: the most effective therapeutic intervention for acute Myocardial infarction is timely effective Myocardial reperfusion thrombolytic therapy or direct percutaneous coronary intervention (PPCI), but the return of Myocardial blood flow to perfusion induces further death of Myocardial cells, a phenomenon known as Myocardial reperfusion injury (IRI), the irreversible consequences of which include Myocardial stunning, reperfusion arrhythmia, microvascular occlusion, intracardial hemorrhage, and fatal Myocardial reperfusion injury, among others. The existing effective measures for preventing and controlling myocardial ischemia-reperfusion injury are very limited, and the clinical prevention and control of myocardial ischemia-reperfusion injury still remains a great challenge.

Current academic thinking holds that sterile inflammation plays a key role in the pathophysiology of myocardial Ischemia Reperfusion Injury (IRI). However, the relevant research reports that cell apoptosis mediated by Gasdermin-D (GSDMD) protein plays a dominant role in aseptic inflammatory response of myocardial ischemia-reperfusion injury. The Gasderm-D (GSDMD) molecule is a cellular apoptosis executive protein that is composed of an N-terminal domain that is co-organized by a stem-loop structure. Normally, the GSDMD protein has no activity, when cells are stimulated by virus, bacteria or Lipopolysaccharide (LPS), through a classical caspase-1 signal path or a non-classical caspase-4/5/11 signal path, a caspase recognition site of Gasderm min-D (GSDMD) is cut, so that an active GSDMD-N-base end is formed, then an N-terminal structural domain is combined with membrane lipid and a pore with the inner diameter of 10-14nm is formed in the membrane, and inflammatory factors such as IL-1 beta and the like can be released outside the cells to cause inflammatory amplification reaction. Therefore, interdomain cleavage of the Gasdermin-D (GSDMD) molecule is a reliable indicator of inflammatory caspase activation and cellular apoptosis. Recent studies have revealed that GSDMD-mediated apoptosis of cardiomyocytes promotes myocardial I/R injury via the caspase-11/GSDMD signaling pathway. Therefore, the development of a mechanism related to the GSDMD and the myocardial ischemia-reperfusion injury and the important significance of the GSDMD serving as a molecular target for resisting the myocardial ischemia-reperfusion injury are realized.

AQ-390, a small molecule substance with potential binding to GSDMD protein obtained by virtual screening in computer. The structure is shown in figure 1. At present, the medical field has no report about the inhibition of cell apoptosis by AQ-390, and no medicine specially aiming at the cell apoptosis is clinically used at present. On one hand, the invention provides a new medicine, a new action mechanism and a new target spot for treating myocardial ischemia-reperfusion injury; on the other hand, a molecular binding mechanism of AQ-390 and cell apoptosis executive molecule GSDMD is disclosed, and a theoretical basis is provided for the application of AQ-390 to the clinical treatment of myocardial ischemia reperfusion injury of PCI patients.

Disclosure of Invention

The invention aims to overcome the blank of medicaments for treating or preventing myocardial ischemia-reperfusion injury of PCI patients and open up the medical application of AQ-390.

The invention provides an application of a small molecular compound AQ-390 in preparing a medicine for resisting cell apoptosis and playing an anti-inflammatory effect to prevent or treat ischemia-reperfusion injury, relates to an application of the small molecular compound AQ-390 in preparing the medicine for treating myocardial ischemia-reperfusion injury, and also relates to an application of the small molecular compound AQ-390 in preparing a GSDMD inhibitor with cell apoptosis resisting activity.

The invention is realized by that a medicine for resisting cell apoptosis and playing an anti-inflammatory effect so as to prevent or treat the myocardial ischemia-reperfusion injury is a small molecule compound AQ-390. The small molecular compound AQ-390 can be used for injection or oral capsules.

The invention also aims to provide an injection (25-50 mg/kg/day) prepared from the medicine for preventing or treating ischemia-reperfusion injury by utilizing the anti-cell apoptosis to play an anti-inflammatory effect.

The invention also aims to provide an oral capsule (25-50 mg/kg/day) prepared from the medicine for preventing or treating ischemia-reperfusion injury by utilizing the anti-cell apoptosis to exert an anti-inflammatory effect.

The invention also aims to provide a GSDMD inhibitor (25-50 mg/kg/day) prepared from the medicine for preventing or treating ischemia-reperfusion injury by utilizing the anti-cell apoptosis to play an anti-inflammatory effect, wherein the GSDMD inhibitor with the anti-cell apoptosis activity is prepared from AQ-390 and pharmaceutically acceptable auxiliary materials.

Further, acceptable excipients are acceptable carriers or fillers or binders or wetting agents or disintegrating agents or absorption promoters or surfactants or adsorption carriers or lubricants or 0.9% sodium chloride ("excipients" means pharmaceutical carriers conventional in the pharmaceutical field, for example, diluents, excipients such as water, etc., fillers such as starch, sucrose, etc., binders such as cellulose derivatives, alginates, gelatin and polyvinylpyrrolidone, wetting agents such as glycerin, disintegrating agents such as agar, calcium carbonate and sodium bicarbonate, absorption promoters such as quaternary ammonium compounds, surfactants such as cetyl alcohol, adsorption carriers such as kaolin and soap clay, lubricants such as talc, calcium/magnesium stearate, polyethylene glycol, etc., the formulation ratio is 0.9% sodium chloride, for example, butylphthalide: 0.9% sodium chloride =1

According to the mass ratio, the mass ratio of AQ-390 to pharmaceutically acceptable auxiliary materials is 1.

The invention also aims to provide a tablet prepared from the GSDMD inhibitor, which is prepared from the medicine for preventing or treating ischemia-reperfusion injury by utilizing the anti-cell apoptosis to exert an anti-inflammatory effect.

The invention also aims to provide a pill prepared from the GSDMD inhibitor, which is prepared from the medicine for preventing or treating ischemia-reperfusion injury by utilizing the anti-cell apoptosis to exert an anti-inflammatory effect.

The invention also aims to provide a suspension prepared from the GSDMD inhibitor, which is prepared from the medicine for preventing or treating ischemia-reperfusion injury by utilizing the anti-cell apoptosis to exert the anti-inflammatory effect.

The invention also aims to provide granules prepared from the GSDMD inhibitor, which is prepared from the medicine for preventing or treating ischemia-reperfusion injury by utilizing the anti-cell apoptosis to exert the anti-inflammatory effect.

The invention also aims to provide an emulsion prepared from the GSDMD inhibitor, which is prepared from the medicine for preventing or treating ischemia-reperfusion injury by utilizing the anti-cell apoptosis to exert the anti-inflammatory effect.

The potential GSDMD small molecule inhibitor AQ-390 is obtained by a virtual screening method. The method is characterized in that a cell apoptosis model is constructed on the THP-1 cells induced by PMA by using stimulation of LPS combined with Nigericin and a sepsis model is constructed by injecting LPS into the abdominal cavity of a mouse, and the result shows that 100 mu MAQ-390 can obviously relieve cell apoptosis, relieve cell damage caused by inflammation and improve the survival rate of a sepsis mouse. Subsequently, the present invention utilizes a biofilm optical coherence Biosensor (BLI), and the protein pulldown technology to find that AQ-390 and GSDMD protein can be directly combined and kinetically stable. In a mouse myocardial ischemia reperfusion animal model, AQ-390 can relieve cell apoptosis, improve myocardial ischemia reperfusion injury, reduce myocardial infarction area, inhibit IL-1 beta and IL-18 expression in myocardial tissues of infarct areas and contents of LDH and CK-MB in blood, and protect myocardial tissues. On a cell level, AQ-390 can obviously improve cell damage caused by an anoxia reoxygenation model constructed by primary myocardial cells of a milk rat within a safe drug concentration range. According to the results, AQ-390 has the function of specifically and targetedly inhibiting GSDMD to resist the inflammatory effect caused by cell apoptosis, thereby relieving myocardial ischemia-reperfusion injury.

In specific application, the medicine is various preparations prepared from AQ-390 and pharmaceutically acceptable auxiliary materials. Wherein, the compound is preferably used in injection and oral capsule. The preparation of the present invention may be in unit dosage forms such as injections, capsules (including sustained release or delayed release forms), tablets, pills, suspensions, granules, tinctures, syrups, emulsions, suspensions and the like, and various sustained release forms, so as to be suitable for various administration modes such as oral administration, parenteral injection, mucosal, intramuscular, intravenous, subcutaneous, intraocular, intradermal or transdermal administration and the like (among which injections for injection and oral capsules are preferred).

The invention is characterized in that the synthesis of active ingredients in the medicine is simple, the specific targeting endothelin (Gasderm D, GSDMD) inhibits cell apoptosis so as to exert good anti-inflammatory activity to prevent or treat ischemia-reperfusion injury, the optimal inhibition concentration is 100 mu M, and the medicine can be used as a treatment medicine for myocardial ischemia-reperfusion injury, sepsis myocardial diseases, atherosclerosis and the like, and has obvious treatment effect.

Drawings

FIG. 1 is a molecular structural formula of a small molecule compound AQ-390 disclosed by the invention.

FIG. 2 is a graph showing the effect of the small molecule compound AQ-390 of the present invention on sepsis and GSDMD mediated apoptosis injury in a macrophage model.

FIG. 3 is a graph showing the results of the binding structure of the small molecule compound AQ-390 and the GSDMD protein and the related molecular mechanism.

FIG. 4 is a graph showing the effect of AQ-390, a small molecule compound, on the damage of hypoxic reoxygenation cells of primary cardiomyocytes.

FIG. 5 is a graph showing the effect of AQ-390, a small molecule compound, on myocardial ischemia reperfusion injury in mice.

FIG. 6 is a graph showing the effect of AQ-390, a small molecule compound, on the degree of apoptosis of myocardial cells of myocardial ischemia-reperfusion injury in mice.

Detailed Description

The following examples are provided to illustrate specific embodiments of the present invention.

Primary cardiomyocytes used in the present invention were extracted from the left ventricle of neonatal Sprague-Dawley (SD) rats in Dulbecco's modified Eagle medium (DMEM, thermo Fisher Scientific, united States), supplemented with 10% fetal bovine serum (FBS, thermo Fisher Scientific) and 1% penicillin-streptomycin (Thermo Fisher Scientific). The Thp-1 macrophages used in the present invention were purchased from American Type Culture Collection (ATCC) and used as RPMI1640 medium supplemented with 10% fetal bovine serum and 1% penicillin-streptomycin. The culture medium, serum and diabody were all commercially available sources and used according to the instructions provided by the manufacturer. Cells were routinely cultured in a CO2 incubator at 37 ℃ 5%. The purified protein of GSDMD used in the present invention was purchased from Hangzhou Huaan Biotechnology Ltd. AQ-390 drugs for use in the present invention were purchased from Specs corporation. The LPS drugs used in the present invention were purchased from Sigma-Aldrich and Nigericin (Nig) from aladdin. The rest of the reagents and materials were also commercially available and used according to the instructions provided by the manufacturer.

Experimental animals: the C57BL/6 male mice used in the present invention were purchased from Uygon laboratory animal technology, inc., zhejiang and raised in the animal laboratory center of the first hospital affiliated to Wenzhou medical university. GSDMD (glutathione S-associated disulfide linker) -Cas9 culture technology ^-/- A mouse. Mice were housed in a constant temperature day and night animal house with a rhythm of 12-12h using standard rodent chow and water. Animals took at least one week to grow acclimatically before the start of the experiment.

Example 1 aq-390 has a resistance to sepsis and to cell pyroptosis damage in a classical pyroptosis model of macrophages

AQ-390 used in the animal experiments of the present invention was formulated to be soluble in 0.25% tween-80 in CMC-Na solution. The solution had a pH of 7.36 and was filtered through a 0.22 microfiltration membrane. Selecting 6-8 week old C57BL/6 healthy mice (WT) and 6-8 week old GSDMD ^-/- Healthy mice are injected with LPS (15 mg/kg) in the abdominal cavity to construct an animal model of sepsis. The AQ-390 drug treatment group constructs a sepsis animal model by injecting LPS (15 mg/kg) with low dose into the abdominal cavity after AQ-390 (25 mg/kg) (25 hours of intraperitoneal injection) pretreatment. Cell experiments Thp-1 macrophages were plated in six well plates in 2ml of medium. A classical model of cell apoptosis was constructed by treating with LPS (10. Mu.g/ml) for 6 hours and Nigericin (Nig) (10. Mu.M) for 1 hour to stimulate macrophages. The AQ-390 drug-treated group pre-treated macrophages for 1 hour for AQ-390 at different drug concentrations, followed by 4 hours of LPS (10. Mu.g/ml) treatment and 1 hour stimulation of macrophages by Nigericin (Nig) (10. Mu.M) to construct a classical cell apoptosis model. At the animal level, we found GSDMD ^-/- Mice were effective against LPS-induced death of septic mice (fig. 2A) relative to wild-type mice, while AQ-390, as a potential small molecule inhibitor of GSDMD, also reduced LPS-induced mortality of septic mice (fig. 2B); at a cellular level, AQ-390 is in a safe drug concentration range, and can effectively improve macrophage activity stimulated by LPS combined with Nigericin (figure 2C), reduce secretion of IL-1 beta and IL-18 (figure 2D), reduce membrane-bound quantity of GSDMDM-NT (figure 2E), improve cell morphology and permeability (figure 2F), and inhibit macrophage apoptosis.

Wherein, FIG. 2A shows GSDMD ^-/- Compared with a Wild Type (WT) mouse, the mouse can effectively resist sepsis death induced by LPS, and the survival time of the mouse is prolonged; FIG. 2B shows that AQ-390 is effective in reducing the mortality of LPS-induced septic mice when AQ-390 treated mice are compared to Wild Type (WT) mice; FIG. 2C shows the effect of the CCK8 assay gradient concentration of the potential small molecule inhibitor AQ-390 on macrophage activity; FIG. 2D shows that AQ-390 reduces IL-1 β and IL-18 levels in cell supernatants of a model that stimulates macrophages with LPS in combination with Nigericin (Nig); FIG. 2E shows the use of PI (Propidium iodide) to measure cell permeabilityObserving the influence of AQ-390 on the form and permeability of macrophages stimulated by LPS combined with Nigericin (Nig) (under the condition that the cell membrane permeability is normal, PI can not permeate into cells, and the cells with the permeability influenced show red fluorescence due to the fact that PI permeates into the cells); FIG. 2F uses cellular immunofluorescence to observe the effect of AQ-390 on the stimulation of GSDMDM-NT production in macrophages by LPS in combination with Nigericin (Nig).

Example 2 aq-390 has a direct binding effect with the GSDMD protein and is kinetically stable

The invention utilizes a biomembrane light coherence Biosensor (BLI) and a protein pulldown technology to analyze the binding relationship between AQ-390 and GSDMD protein: the biofilm coherent biosensor utilizes a ForteBio Octet detection method, and mainly adopts a full-automatic test platform produced by ForteBio, namely an Octet RED96 intermolecular interaction detection system to evaluate the binding effect of AQ-390 and GSDMD protein. GST-labeled GSDMD purified protein (GST-GSDMD) and GST-tagged protein (GST) were diluted to 10. Mu.g/mL, respectively, using PBS Buffer (pH 7.4) in volumes of 400. Mu.L, respectively; AQ-390 was diluted to 1000. Mu.M using 5% DMSO + PBST 2.4 PBS +0.02% to a maximum concentration, diluted in duplicate to 6 concentrations for subsequent testing; GST-GSDMDM and GST were immobilized using GST probe (ForteBio, 18-5096); the samples and reagents are sequentially placed in a sample plate, an Octet RED96 program is used for operation, a fortebio data analysis 10.0 software is used for adopting a double-deduction calculation mode, namely, a buffer solution signal and a GST combined signal are deducted, then, the deducted signal data are subjected to Align processing, baseline 55-59.8s (the starting point of the combined signal is subjected to zero processing, 60s signals in the Baseline step are subjected to zero processing, the experimental flow with complete interaction is Baseline 60s, combined 60s and dissociated 60 s), and finally, the obtained data are subjected to fitting analysis (a fitting model 1. For the Pulldown experiments, beaverbedardTM streptavidin-agarose beads and biotinylated AQ-390 were used in the present invention. mu.L of 1mM biotinylated AQ-390 was added to 10. Mu.L of streptavidin-agarose beads, using biotin, non-biotinylated AQ-390 and untreated beads alone as controls, then GSDMD purified protein was added to streptavidin-agarose beads with Bio-AQ-390, the mixture was incubated for 3 hours at 25 ℃ with gentle shaking, then the samples were washed 3 times, the protein was eluted by boiling 5 Xloading buffer, and the samples were loaded in groups on 10% polyacrylamide gel for Western Blot analysis. According to BLI and pulldown experiment related data analysis, AQ-390 can be combined with the purified protein of GSDMD and has stable kinetics (FIGS. 3B and C).

Wherein, FIG. 3A shows a schematic representation of the protein binding sites of AQ-390 and GSDMD; FIG. 3B is a schematic diagram showing the results of the experiments on biotinylated AQ-390 and GSDMD purified protein pulldown; FIG. 3C is a graph showing the results of AQ-390 and GSDMD purified protein BLI.

Example 3, AQ-390 can inhibit GSDMD protein in a targeted manner to relieve cell apoptosis and relieve myocardial ischemia-reperfusion injury

Cell layer: rat primary cardiomyocytes were cultured in sugar-free and serum-free DMEM cell culture medium for 2 hours in a hypoxia workstation (1% O2, 5% CO2, about 95% N2), and then the groups of cells were re-oxygenated in an normoxic incubator for 4 hours to construct a cardiomyocyte model with hypoxia-reoxygenation injury. The AQ-390 drug-treated group was prepared by pretreating cardiomyocytes with a dose of AQ-390 within a safe range for 1 hour, placing the cells in a sugar-free and serum-free DMEM cell culture medium, culturing the cells in a hypoxia workstation (1% O2, 5% CO2, about 95% N2) for 2 hours, and then placing the cells in an normoxic incubator for 4 hours to re-oxygenate the cells, respectively, to construct a cardiomyocyte model of hypoxia-reoxygenation injury. The specific cell experiment groups are: normal control group, drug-only treatment group, H/R group, AQ-390 (100. Mu.M) + H/R group, AQ-390 (200. Mu.M) + H/R group (reason for selecting 100. Mu.M, 200. Mu.M AQ-390 drug concentration is illustrated by the following FIG. 4B).

Animal layer: selecting healthy male C57BL/6 mice of 6-8 weeks old (related animal information is described in detail earlier), wherein the average weight is 20-24g, the mice adopt isoflurane, the left anterior descending branch is ligated by using 5-0 thin lines after the chest is opened after the breathing is stable, the left ventricular wall is observed to be whitened, the chest is closed after the slipknot is left, and the sample is taken after the slipknot is loosened and the infusion is carried out for 4 hours after 30 minutes. Sham (Sham) groups thread but not ligate vessels after thoracotomy. 25mg/kg and 50mg/kg of AQ-390 were intraperitoneally injected 4 hours before molding, and 8 animals per group were intraperitoneally injected with normal saline in the control group. Mice at 6-8 weeks were randomized into 5 groups: sham group (Sham), AQ-390 (50 mg/kg) + Sham group, I/R group, AQ-390 (25 mg/kg) + I/R group, AQ-390 (50 mg/kg) + I/R group.

In the cell level, the invention firstly tests whether different concentrations of AQ390 drugs can influence the activity of primary cardiomyocytes per se, and any final concentration of AQ390 between 0 and 400. Mu.M can not influence the activity of primary cardiomyocytes. Therefore, the present invention finally selects drug concentrations of 100. Mu.M and 200. Mu.M for subsequent experiments (FIG. 4A). Then, the invention observes the myocardial cells under a light microscope, finds that the hypoxic myocardial cell structure is disordered, the fusiform myocardial cells are elongated and thinned, the cell activity is reduced, the release of LDH and IL-18 is increased, the myocardial cell morphology is improved after the AQ390 medicament pretreatment, the cell activity is also improved, the release of LDH and IL-18 is reduced, and a certain dose dependence is presented. The morphology and activity of the cardiomyocytes in the control group were not significantly changed (fig. 4B, C, D, E).

In the animal level, evans Blue/TTC staining is used for observing the myocardial infarction area, and the myocardial infarction area is improved in the non-perfusion group dose dependence treated by the two drug concentrations (figures 5A, B and C), which shows that AQ390 can protect the heart tissue subjected to ischemia-reperfusion and reduce the myocardial infarction area. The invention detects LDH (figure 6A) and CK-MB (figure 6B) in the serum of each group of mice, IL-1 beta and IL-18 (figure 6C and D) in the heart tissue of the mice, and analyzes IL-1 beta and IL-18 (figure 6E and F) in the heart tissue of the mice by a qPCR method, and the obtained result can show that AQ390 can improve myocardial ischemia reperfusion injury caused by GSDMD mediated cell apoptosis.

Wherein, FIG. 4A shows the effect of AQ-390 on the morphology of primary cardiomyocytes in the hypoxia reoxygenation model observed by an optical microscope; FIG. 4B shows the effect of the potential small molecule inhibitor AQ-390 in the gradient concentration on the activity of primary cardiomyocytes in dairy rats, measured using CCK-8; FIG. 4C shows that AQ-390 significantly improves cell viability of primary cardiomyocytes following hypoxia reoxygenation in a dose-dependent manner; FIG. 4D shows that AQ-390 significantly dose-dependently reduced the amount of LDH released in the cell supernatant after hypoxia reoxygenation of primary cardiomyocytes; FIG. 4E shows that AQ-390 significantly dose-dependently reduced the amount of IL-18 released from the cell supernatant after hypoxia reoxygenation of primary cardiomyocytes.

Wherein, the myocardial ischemia reperfusion model of the mice is constructed as shown in FIG. 5A, and the influence of AQ-390 on the myocardial infarction area is observed according to Evans Blue/TTC staining (generally, a white area is adopted to represent an infarct area, a red area represents an ischemia risk area, and a Blue area represents a non-ischemia area (the figure is changed from white to red and Blue in sequence from left to right), FIG. 5B is a percentage statistical chart of the ischemia risk areas of the hearts of five groups of mice (AAR: ischemia risk area; LV: left ventricle area), and FIG. 5C is a percentage statistical chart of the myocardial infarction areas of five groups of mice (IFN: infarct area; AAR: ischemia risk area).

Wherein, FIG. 6A shows AQ-390 dose-dependently decreasing LDH levels in serum of I/R mice; FIG. 6B shows that AQ-390 decreases the level of myocardial injury indicator CK-MB in the serum of the group of I/R animals; FIGS. 6C and D show the dose-dependent reduction of IL-1 β and IL-18 expression in myocardial tissues in infarct areas of I/R mice by AQ-390; FIGS. 6E and F show the detection of the expression levels of IL-1. Beta. And IL-18 in myocardial tissues in infarct areas of mice in each group by the qPCR method. AQ-390 can reduce the expression quantity of IL-1 beta and IL-18 in myocardial tissues of infarct areas of I/R mice in a dose-dependent manner.

The preparation method of the medicine for treating or preventing myocardial ischemia-reperfusion injury provided by the embodiment of the invention comprises the following steps: various dosage forms of the pharmaceutical composition of the present invention can be prepared according to conventional production methods in the pharmaceutical field. For example, the active ingredient AQ-390 can be mixed with one or more carrier excipients and then made into the required dosage forms, such as injections, capsules, tablets and the like.

It will be apparent to those skilled in the art that various changes and modifications may be made in the present invention without departing from the spirit and scope of the invention. Thus, if such modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include such modifications and variations.

Claims (3)

1. The application of the small molecule compound AQ-390 in the preparation of the medicine for resisting cell apoptosis is characterized in that: the application of the small molecule compound AQ-390 in the preparation of the medicine for preventing or treating myocardial ischemia-reperfusion injury by playing an anti-inflammatory effect on resisting cell apoptosis, wherein the structural formula of the small molecule compound AQ-390 is as follows:

。

2. use according to claim 1, characterized in that: the medicine is injection.

3. Use according to claim 1, characterized in that: the medicine is an oral capsule.

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