Anti-pyroptosis polypeptides and their applications

Abstract

The present invention discloses an anti - pyroptosis polypeptide and its application, relating to the technical field of biomedicine. The key points of its technical solution are: the anti - pyroptosis polypeptide is specifically used in the preparation of drugs for preventing and treating atherosclerosis. The amino acid sequence of the anti - pyroptosis polypeptide is shown as SEQ ID NO.1. The present invention firstly uses the anti - pyroptosis polypeptide to prepare drugs for treating and / or preventing atherosclerosis, and the effect of the anti - pyroptosis polypeptide in controlling atherosclerosis has been verified in cell models and animal models. In particular, the anti - pyroptosis polypeptide can enhance the viability of endothelial cells in the state of defective pyroptosis, significantly inhibit the expression of pyroptosis - related genes and proteins, and at the same time can reduce the levels of serum cholesterol and low - density lipoprotein in atherosclerotic mice, and reduce aortic lipid deposition and plaque formation. Moreover, when the anti - pyroptosis polypeptide of the present invention is used as a drug ingredient, it also has advantages such as low toxicity, small molecular weight, low immunogenicity and high druggability.

Description

Technical Field

[0001] The present invention relates to the field of biomedical technology, and more specifically, to anti-pyroptosis polypeptides and their applications. Background Art

[0002] Atherosclerosis (AS) is a chronic inflammatory disease based on dyslipidemia and inflammation. Cardiovascular diseases (CVDs) with AS as the common pathological basis are the leading cause of death in the elderly. In recent years, the deaths caused by CVDs due to AS have continued to increase and show a trend of younger age, and the existing anti-AS drugs cannot meet the growing needs of patients. Therefore, there is an urgent need to seek new anti-atherosclerotic strategies.

[0003] Due to their low toxicity, small molecular weight, good targeting, and easy entry into cells, polypeptides have become a major trend in the research and development of biopharmaceuticals. In the diagnosis and treatment of cardiovascular diseases, research on polypeptides has had extensive clinical applications. For example: Polypeptide drugs for the treatment of cardiovascular diseases have been approved for marketing, such as the platelet glycoprotein IIb / IIIa receptor antagonist eptifibatide (INTEGRILIN, trade name Han'an), and the polypeptide drug recombinant human B-type natriuretic peptide (rhBNP, trade name Xinhuosu) acting on the natriuretic peptide receptor. Existing research results show that polypeptides have great potential and broad application prospects in the field of cardiovascular disease diagnosis and treatment. In recent years, the application of the GLP-1 peptide analogue liraglutide in the clinical treatment of diabetes has injected a boost into the research and development and translational research of polypeptide drugs.

[0004] The anti-pyroptosis polypeptide is a newly discovered polypeptide sequence in the pyroptotic endothelial cell model through polypeptideomics technology, and there are no relevant reports at home and abroad. Summary of the Invention

[0005] The purpose of the present invention is to provide anti-pyroptosis polypeptides and their applications, and solve the technical problems mentioned in the background art.

[0006] The above technical purpose of the present invention is achieved through the following technical solutions: an anti-pyroptosis polypeptide, and the amino acid sequence of the anti-pyroptosis polypeptide is SEQ ID NO.1.

[0007] An equivalent alternative to the above solution is: the amino acid sequence of the anti-pyroptosis polypeptide has at least 70% homology with SEQ ID NO.1.

[0008] Furthermore, the anti-pyroptosis polypeptide is synthesized by a biological method.

[0009] Furthermore, the anti-pyroptosis polypeptide is synthesized by a chemical method.

[0010] The present invention also provides the use of the anti-pyroptosis polypeptide in the preparation of a medicament for preventing and treating atherosclerosis.

[0011] The medicament comprises the anti-pyroptosis polypeptide and a pharmaceutical adjuvant.

[0012] Furthermore, the dosage form of the medicament is one of tablets, granules, pills, powders, capsules, injections, oral liquids, ophthalmic preparations and external preparations.

[0013] Furthermore, the adjuvant is selected from at least one of fillers, wetting agents, binders, disintegrants, lubricants, color, flavor and odor regulators, solvents, solubilizers, cosolvents, emulsifiers, antioxidants, metal complexing agents, inert gases, bacteriostatic agents, local anesthetics, pH regulators, isotonic or isosmotic regulators.

[0014] Furthermore, the filler is selected from at least one of starches, sugars, fibrous substances and inorganic salts; the wetting agent is selected from at least one of purified water and ethanol; the binder is selected from at least one of starch paste, dextrin, sugar powder and syrup, cellulose derivatives, gelatin, polyvinylpyrrolidone and polyethylene glycol; the disintegrant is selected from at least one of dry starch, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, cross-linked carboxymethyl cellulose sodium, cross-linked polyvinylpyrrolidone, surfactants, effervescent disintegrants; the lubricant is selected from at least one of talc, calcium stearate, magnesium stearate, magnesium lauryl sulfate, colloidal silica and polyethylene glycol; the color, flavor and odor regulator is selected from at least one of pigments, flavors, spices, sweeteners, mucilage and odor correctors; the solvent is selected from at least one of water for injection, injection oil, ethanol, glycerol, propylene glycol, polyethylene glycol, dimethyl sulfoxide, liquid paraffin, fatty oil and ethyl acetate; the solubilizer is selected from at least one of Tweens, Myrj, polyoxyethylene fatty alcohol ethers, soaps, sulfates, sulfonates; the cosolvent is selected from at least one of organic acids and their salts, amides and amine compounds, inorganic salts, polyethylene glycol, polyvinylpyrrolidone, glycerol.

[0015] Further, the emulsifier is selected from at least one of span, tween, myrj, benzalkonium, glycerol fatty acid ester, higher fatty acid salt, sulfate, sulfonate, acacia, tragacanth, gelatin, pectin, phospholipid, agar, sodium alginate, hydroxide, silicon dioxide and bentonite; the suspending agent is selected from at least one of glycerol, syrup, acacia, tragacanth, agar, sodium alginate, cellulose derivative, polyvinylpyrrolidone, carbopol, glucose, polyvinyl alcohol and thixotropic gel; the antioxidant is selected from at least one of sulfite, metabisulfite, bisulfite, ascorbic acid, gallic acid and its esters; the metal chelating agent is selected from one of disodium ethylenediaminetetraacetate and polycarboxylic acid compounds; the inert gas is selected from one of nitrogen and carbon dioxide; the bacteriostatic agent is selected from at least one of parabens, organic acids and their salts, quaternary ammonium compounds, chlorhexidine acetate, alcohols, phenols and volatile oils; the local anesthetic is selected from at least one of benzyl alcohol, chlorobutanol, lidocaine and procaine; the pH regulator is selected from at least one of hydrochloric acid, sulfuric acid, phosphoric acid, citric acid, tartaric acid, acetic acid, sodium hydroxide, sodium bicarbonate, ethylenediamine, meglumine, phosphate, acetate and citrate; the isotonic or isosmotic regulator is selected from at least one of glucose, sodium chloride, sodium citrate, sorbitol and xylitol.

[0016] This solution relates to the following sequences:

[0017] SEQ ID NO.1:

[0018] Its general formula is: X-P-Y, where P is:

[0019] Gly-Gln-Gly-Gly-Ala-Gly-Pro-Val--Gly-Gly-Gln-Gly—Pro-Arg-Gly-Met-Gly-Pro (GQGGAGPVGGQGPRGMGP) (ASRP2).

[0020] In summary, the present invention has the following beneficial effects: The present invention first uses the anti-pyroptosis polypeptide to prepare a drug for treating or / and preventing atherosclerosis, and the effect of the anti-pyroptosis polypeptide in treating atherosclerosis has been verified in cell models and animal models. In particular, the anti-pyroptosis polypeptide can enhance the viability of pyroptosis-induced human umbilical vein endothelial cells, significantly inhibit the activation of pyroptosis-related proteins, and at the same time can reduce the levels of cholesterol and low-density lipoprotein in the serum of atherosclerotic mouse models, and reduce lipid deposition and plaque area in the aortic root; moreover, when the anti-pyroptosis polypeptide of the present invention is used as a drug ingredient, it also has advantages such as low toxicity, small molecular weight, low immunogenicity and high drug-forming property. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1It is the mass spectrometry diagram of the anti - pyroptosis polypeptide in Example 1 of the present invention;

[0022] Figure 2 It is the test result diagram of the viability of human umbilical vein endothelial cells (HUVEC) in each group in Example 3 of the present invention;

[0023] Figure 3 It is the test result diagram of the pyroptosis - related gene levels of human umbilical vein endothelial cells (HUVEC) in each group in Example 3 of the present invention;

[0024] Figure 4 It is the fluorescence result diagram of pyroptosis - related proteins Caspase1 and TUNEL of human umbilical vein endothelial cells (HUVEC) in each group in Example 3 of the present invention;

[0025] Figure 5 A is the test result diagram of the effect of the anti - pyroptosis polypeptide on the serum low - density lipoprotein level in atherosclerotic mice in Example 4 of the present invention;

[0026] Figure 5 B is the test result diagram of the effect of the anti - pyroptosis polypeptide on the serum total cholesterol level in atherosclerotic mice in Example 4 of the present invention;

[0027] Figure 6 It is the result diagram of the effect of the anti - pyroptosis polypeptide on the plaque area and lipid deposition in each group of atherosclerotic mice in Example 4 of the present invention. Detailed implementation mode

[0028] The following is a further detailed description of the present invention in conjunction with the attached Figures 1-6 Make a further detailed description of the present invention.

[0029] Example 1: An anti - pyroptosis polypeptide, the amino acid sequence of the anti - pyroptosis polypeptide is shown in SEQ ID NO.1: Its general formula is: X - P - Y, where P is:

[0030] Gly - Gln - Gly - Gly - Ala - Gly - Pro - Val--Gly - Gly - Gln - Gly—Pro - Arg - Gly - Met - Gly - Pro(NH3 - GQGGAGPVGGQGPRGMGP - OH)(ASRP2); This ASRP2 polypeptide has 18 amino acids, located at amino acids 668 - 685 of human SFPQ protein, with an isoelectric point (PI) of 9.75, a molecular mass (MW) of 1535.7263, a half - life of 30h, and an instability index of 15.52, indicating that this polypeptide is relatively stable.

[0031] X is: NH3 or any one amino acid or a combination of any two amino acids;

[0032] Y is: OH or any one amino acid or a combination of any two amino acids;

[0033] It is chemically synthesized by solid phase by Shanghai Kopeptide Biotechnology Co., Ltd., and the purity is above 95%.

[0034] An alternative equivalent to the above technical solution is that the amino acid sequence of the anti-pyroptosis polypeptide has at least 70% homology with SEQ ID NO.1.

[0035] Example 2: It relates to a new application of the anti-pyroptosis polypeptide, specifically to the application of the anti-pyroptosis polypeptide in the preparation of a drug for preventing and / or treating heart diseases. The drug contains the anti-pyroptosis polypeptide and pharmaceutically acceptable excipients, and the drug includes but is not limited to intravenous injection, intraperitoneal injection, intramuscular injection, subcutaneous injection, oral administration, sublingual administration, nasal administration, transdermal administration, etc.

[0036] In this example, the dosage form of the drug is not particularly limited, including but not limited to tablets, granules, pills, powders, capsules, injections, oral liquids, ophthalmic preparations, topical preparations, etc.

[0037] In this example, the types of excipients are not particularly limited, including but not limited to the following types: fillers, wetting agents, binders, disintegrants, lubricants, color, flavor and odor regulators, solvents, solubilizers, cosolvents, emulsifiers, antioxidants, metal complexing agents, inert gases, bacteriostatic agents, local anesthetics, pH regulators, isotonic or isosmotic regulators, etc.

[0038] Wherein the filler is selected from at least one of starches, sugars, fibrous substances, and inorganic salts; and / or, the wetting agent is selected from at least one of purified water and ethanol; and / or, the binder is selected from at least one of starch paste, dextrin, powdered sugar and syrup, cellulose derivatives, gelatin, polyvinylpyrrolidone, and polyethylene glycol; and / or, the disintegrant is selected from at least one of dry starch, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, cross-linked carboxymethyl cellulose sodium, cross-linked polyvinylpyrrolidone, surfactants, and effervescent disintegrants; and / or, the lubricant is selected from at least one of talc, calcium stearate, magnesium stearate, magnesium lauryl sulfate, colloidal silica, and polyethylene glycol; and / or, the color, flavor, and odor regulator is selected from at least one of pigments, flavors, spices, sweeteners, mucilage agents, and odor correctors; and / or, the solvent is selected from at least one of water for injection, injection oil, ethanol, glycerol, propylene glycol, polyethylene glycol, dimethyl sulfoxide, liquid paraffin, fatty oil, and ethyl acetate; and / or, the solubilizer is selected from at least one of Tweens, Myrj, polyoxyethylene fatty alcohol ethers, soaps, sulfates, and sulfonates; and / or, the cosolvent is selected from at least one of organic acids and their salts, amides and amine compounds, inorganic salts, polyethylene glycol, polyvinylpyrrolidone, and glycerol; and / or, the emulsifier is selected from at least one of Spans, Tweens, Myrj, Brij, glycerol fatty acid esters, higher fatty acid salts, sulfates, sulfonates, gum arabic, tragacanth, gelatin, pectin, phospholipids, agar, sodium alginate, hydroxides, silicon dioxide, and bentonite; and / or, the suspending agent is selected from at least one of glycerol, syrup, gum arabic, tragacanth, agar, sodium alginate, cellulose derivatives, polyvinylpyrrolidone, carbopol, glucose, polyvinyl alcohol, and thixotropic gel; and / or, the antioxidant is selected from at least one of sulfites, metabisulfites, bisulfites, ascorbic acid, gallic acid and its esters; and / or, the metal chelating agent is selected from one of disodium ethylenediaminetetraacetate and polycarboxylic compounds; and / or, the inert gas is selected from one of nitrogen and carbon dioxide; and / or, the bacteriostatic agent is selected from at least one of parabens, organic acids and their salts, quaternary ammonium compounds, chlorhexidine acetate, alcohols, phenols, and volatile oils; and / or, the local anesthetic is selected from at least one of benzyl alcohol, chlorobutanol, lidocaine, and procaine; and / or, the pH regulator is selected from at least one of hydrochloric acid, sulfuric acid, phosphoric acid, citric acid, tartaric acid, acetic acid, sodium hydroxide, sodium bicarbonate, ethylenediamine, meglumine, phosphates, acetates, and citrates; and / or, the isotonic or isosmotic regulator is selected from at least one of glucose, sodium chloride, sodium citrate, sorbitol, and xylitol.

[0039] On the basis of defining the amino acid sequence composition of the anti-pyroptosis polypeptide in this example, the preparation method of the anti-pyroptosis polypeptide is not particularly limited. It can be by chemical synthesis or by biosynthesis. Chemical synthesis methods include, but are not limited to: solid-phase synthesis method, liquid-phase synthesis method, and other polypeptide synthesis methods including N-carboxyanhydride method (NCA) of amino acids and combinatorial chemistry method. Biosynthesis methods include, but are not limited to: fermentation method, enzymatic hydrolysis method, genetic engineering method, etc.

[0040] Example 3: Cell experiment

[0041] 1. Experimental cells: Human umbilical vein endothelial cells HUVEC, purchased from ATCC;

[0042] 2. Method for inducing cell pyroptosis:

[0043] 1) HUVECs were inoculated in six-well plates and cultured in DMEM medium until the density reached 80%;

[0044] 2) Group treatment of HUVECs cells:

[0045] A. HUVECs were changed to sugar-free and serum-free DMEM medium without any treatment, counted as the Control group (Group C);

[0046] B. HUVECs were cultured for 20 h after fusion, then treated with LPS for 3.5 h, and then continued to be treated with 5 mmol / L ATP for 0.5 h, counted as the LPS+ATP (L / A) group;

[0047] C. HUVECs were pretreated with ASRP2 polypeptide at a final concentration of 1 μmol / L for 20 h, then treated with LPS for 3.5 h, and 5 mmol / L ATP was added for 0.5 h, counted as the LA+ASRP2 1 μmol / L [L / A+A2(1 μM)] group;

[0048] D. HUVECs were pretreated with ASRP2 polypeptide at a final concentration of 10 μmol / L for 20 h, then treated with LPS for 3.5 h, and then 5 mmol / L ATP was added for 0.5 h. Counted as the L / A+ASRP2 10 μmol / L (L / A+A2(10 μM)) group.

[0049] 3. Experimental method

[0050] 3.1 Detection of cell viability

[0051] HUVECs cells were seeded in 96-well plates. After treatment according to the above pyroptosis induction method, detection was carried out following the steps of the cck-8 detection kit. 10 μl of cck-8 reagent was added to each well in the 96-well plate. After incubation at 37 °C in the dark for 2 h, the absorbance at 450 nm was measured using an enzyme-linked immunosorbent assay (ELISA) reader.

[0052] 3.2 Detection of pyroptosis-related gene expression

[0053] (1) HUVECs cells were seeded in 6-well plates. After treatment according to the above pyroptosis induction method, total RNA was extracted from the above cultured cells using TRIzol reagent (Invitrogen, Carlsbad, USA) according to the instructions.

[0054] (2) The RNA concentration was determined using a Bio-rad ultraviolet spectrophotometer.

[0055] (3) Total RNA (1 μg) was reverse transcribed using the Prime Script RT kit to synthesize the primers for the target genes. GAPDH was used as an endogenous control for gene expression analysis.

[0056] (4) Quantitative RT-PCR was performed using a Bio-Rad CFX instrument. The PCR cycling conditions were as follows: pre-denaturation at 95 °C for 3 min, 94 °C for 5 s, 58 °C for 15 s, 72 °C for 15 s, 40 cycles, and extension at 72 °C for 30 s. The threshold cycle Ct value was defined as the cycle number at which the fluorescence passed through a fixed threshold.

[0057] 3.3 Immunofluorescence

[0058] (1) Cells were grown on coverslips. After treatment according to the above pyroptosis induction method, they were fixed with paraformaldehyde.

[0059] (2) Serum blocking: BSA was added and incubated for 30 min.

[0060] (3) Caspasel antibody was added and incubated overnight; Caspase1 (1:1000, Abcam).

[0061] (4) The coverslips were washed, and the secondary antibody was added: The coverslips were placed in PBS (PH7.4) and shaken on a shaker for 3 washes, and the secondary antibody was added and incubated at room temperature for 60 min.

[0062] (5) PI was used to counterstain the cell nuclei: PI staining solution was added and incubated at room temperature in the dark for 10 min.

[0063] (6) Autofluorescence quenching: Autofluorescence quenching agent was added for 5 min, and then washed with running water for 10 min.

[0064] (7) Mounting: The coverslips were mounted with an anti-fluorescence quenching mounting medium.

[0065] (8) Microscopic examination and photography: The sections are placed under a scanner to collect images or photographed under a fluorescence microscope; The excitation wavelength of FITC is 465 - 495 nm, and the emission wavelength is 515 - 555 nm, emitting green light; The excitation wavelength of PI CY3 is 510 - 560, and the emission wavelength is 590 nm, emitting red light. The cell nuclei stained by DAPI are blue under ultraviolet excitation, and the positive expression of Caspasel is the green light of the corresponding fluorescein label.

[0066] 3.4 TUNEL staining

[0067] (1) Cell slides are prepared. After being treated by the above pyroptosis induction method, they are fixed with paraformaldehyde.

[0068] (2) Incubate with the TUNEL reaction solution.

[0069] (3) DAPI counterstains the cell nuclei: Add DAPI staining solution and incubate at room temperature in the dark for 10 min.

[0070] (4) Spontaneous fluorescence quenching: Add the spontaneous fluorescence quenching agent for 5 min and rinse with running water for 10 min.

[0071] (5) Sealing the slides: Seal the slides with an anti-fluorescence quenching mounting medium.

[0072] (6) Microscopic examination and photography: The sections are placed under a scanner to collect images or photographed under a fluorescence microscope. The excitation wavelength of FITC is 465 - 495 nm, and the emission wavelength is 515 - 555 nm, emitting green light; The cell nuclei stained by DAPI are blue under ultraviolet excitation.

[0073] 4. Experimental results

[0074] 4.1 Anti-pyroptosis polypeptide improves the viability of cells after pyroptosis injury

[0075] By applying a CCK-8 detection kit, the mitochondrial dehydrogenase in living cells is detected to indirectly reflect the number of living cells. Figure 1 This is the result of the viability test of HUVECs cells in Example 2. According to Figure 2 It can be seen that: Compared with the control group (Ctr group), the number of living cells in the LPS + ATP group (L / A group) decreased significantly (P < 0.01), while the number of living cells in the LPS + ATP plus polypeptide group (L / A + ASRP2 10 μM) increased significantly compared with the L / A group (P < 0.01). In summary, this anti-pyroptosis polypeptide can effectively improve the survival rate of HUVECs endothelial cells induced by pyroptosis. The polypeptide alone group has no significant effect on the number of living cells.

[0076] 4.2 Anti-pyroptosis polypeptide reduces the expression levels of pyroptosis-related genes in HUVECs cells

[0077] Detect the expression of pyroptosis-related genes in cells by PCR method.Figure 3 are the results of Example 2 on the expression of genes related to pyroptosis in HUVECs; among them, Figure 3 are the expression conditions of genes related to pyroptosis, including CASP1, PYCAD, IL-1β, IL-18, and GSDMD. According to the results, the genes related to pyroptosis were significantly increased in the L / A group compared with the Ctr group ((P<0.01). In the polypeptide group, especially the L / A+polypeptide group (10 μM), it was significantly decreased (P<0.01), and showed a dose-dependent manner. The results showed that the polypeptide could significantly inhibit the expression of genes related to pyroptosis and had a protective effect on HUVEC cells.

[0078] 4.3 Anti-pyroptosis polypeptide inhibits the expression of proteins related to pyroptosis in HUVECs and promotes chromatin integrity

[0079] Cell pyroptosis mainly depends on the caspase-1 pathway to sense danger through inflammasomes, recruit and activate caspase-1. Caspase-1 cleaves and activates inflammatory factors such as IL-18 and IL-1β, and cleaves the N-terminal sequence of GSDMD, enabling it to bind to the membrane to form membrane pores, leading to cell swelling, cytoplasmic outflow, and ultimately causing the cell membrane to rupture and cell pyroptosis.

[0080] The results showed that the immunofluorescence results showed that the expression of Caspase1 related to pyroptosis was significantly increased in the L / A group compared with the Ctr group. At the same time, the TUNEL results showed that significant cell death occurred in the L / A group. The anti-pyroptosis peptide group could significantly inhibit Caspase1 expression and cell death.

[0081] Example 4: Animal experiment

[0082] 1. Experimental animals: apoE - / - mice, SPF, body weight: 20 g - 25 g, provided by Jiangsu Jicui Yakang Biotechnology Co., Ltd., and raised in the SPF animal house of Chengdu Lead Discovery Co., Ltd.;

[0083] 2. Experimental grouping: The apoE - / - mice were randomly divided into three groups: 10 mice in the high-fat diet group (HFD group), 10 mice in the high-fat diet + low-dose anti-pyroptosis polypeptide group (5 mg / kg), and 10 mice in the high-fat diet + high-dose anti-pyroptosis polypeptide group (10 mg / kg). The polypeptide was administered by tail vein injection, and the solution was prepared with physiological saline as the solvent;

[0084] 3. Experimental results

[0085] 3.1 Anti-pyroptosis polypeptide reduces the serum LDL and TC contents in atherosclerotic mice;

[0086] As Figure 5As shown in A, compared with the control group, the serum LDL content of the mice in the model group increased significantly (P < 0.01), and the anti - pyroptosis peptide could significantly reduce the serum LDL content. Figure 5 The results in B showed that, compared with the control group, the serum TC content of the mice in the model group increased significantly, and the anti - pyroptosis polypeptide could significantly reduce the serum TC content. Moreover, the lipid - lowering effect of the anti - pyroptosis polypeptide was dose - dependent. In summary, the anti - pyroptosis polypeptide could significantly reduce the contents of LDL and TC in the serum, and this effect was dose - dependent.

[0087] 3.2 Effect of the polypeptide on reducing atherosclerotic lipid deposition and plaque formation

[0088] As Figure 6 shown by the HE staining results in A, the plaque area at the aortic root of the mice in the model group increased significantly (P < 0.01), and the anti - pyroptosis polypeptide could significantly reduce the plaque area at the aortic root (P < 0.01); according to Figure 6 the results in B, the lipid deposition at the aortic root of the mice in the model group increased significantly (P < 0.01), and the anti - pyroptosis polypeptide could significantly reduce the lipid deposition at the aortic root (P < 0.01). In summary, this polypeptide could reduce the plaque area and lipid deposition at the aortic root of atherosclerotic mice, showing an obvious anti - atherosclerotic effect.

[0089] This specific embodiment is only an explanation of the present invention and is not a limitation thereof. After reading this specification, those skilled in the art can make modifications to this embodiment without creative contributions as needed, but as long as it is within the scope of the claims of the present invention, it is protected by the patent law.

Claims

1. An anti-pyroptosis polypeptide, characterized in that: The amino acid sequence of the anti-pyroptosis polypeptide is shown in SEQ ID NO.

1.

2. Use of the anti-pyroptosis polypeptide according to claim 1 in the preparation of a drug for preventing and / or treating atherosclerosis and hyperlipidemia.

3. The application according to claim 2, wherein: The drug comprises the anti-pyroptosis polypeptide and a pharmaceutical excipient.

4. The application according to claim 2, characterized in that: The dosage form of the drug is one of tablets, granules, pills, powders, capsules, injections, oral liquids and ophthalmic preparations.

5. The application according to claim 2, wherein: The dosage form of the drug is an external preparation.

6. The application according to claim 3, characterized in that: The excipient is selected from at least one of fillers, wetting agents, binders, disintegrants, lubricants, color, flavor and fragrance regulators, solvents, solubilizers, cosolvents, emulsifiers, antioxidants, metal complexing agents, inert gases, bacteriostatic agents, local anesthetics, pH regulators, isotonic or isosmotic regulators.

7. Use of the anti-pyroptosis polypeptide according to claim 6 in the preparation of a drug for preventing and treating atherosclerosis, characterized in that: The filler is selected from at least one of starches, sugars, fibrous substances and inorganic salts; the wetting agent is selected from at least one of purified water and ethanol; the binder is selected from at least one of starch paste, dextrin, sugar powder and syrup, cellulose derivatives, gelatin, polyvinylpyrrolidone and polyethylene glycol; the disintegrant is selected from at least one of dry starch, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, cross-linked carboxymethyl cellulose sodium, cross-linked polyvinylpyrrolidone, surfactants, effervescent disintegrants; the lubricant is selected from at least one of talc powder, calcium stearate, magnesium stearate, magnesium lauryl sulfate, colloidal silica and polyethylene glycol; the color, flavor and fragrance regulator is selected from at least one of pigments, flavors, spices, sweeteners, mucilage and odor correctors; the solvent is selected from at least one of water for injection, injection oil, ethanol, glycerol, propylene glycol, polyethylene glycol, dimethyl sulfoxide, liquid paraffin, fatty oil and ethyl acetate; the solubilizer is selected from at least one of Tween series, Myrj series, polyoxyethylene fatty alcohol ethers, soaps, sulfates, sulfonates; the cosolvent is selected from at least one of organic acids and their salts, amides and amine compounds, inorganic salts, polyethylene glycol, polyvinylpyrrolidone, glycerol.

8. The application according to claim 6, characterized in that: The emulsifier is selected from at least one of span, tween, myrj, benzalkonium, glycerol fatty acid ester, higher fatty acid salt, sulfate, sulfonate, gum arabic, tragacanth, gelatin, pectin, phospholipid, agar, sodium alginate, hydroxide, silicon dioxide and bentonite; the antioxidant is selected from at least one of sulfite, metabisulfite, bisulfite, ascorbic acid, gallic acid and its esters; the metal chelating agent is selected from one of disodium ethylenediaminetetraacetate and polycarboxylic acid compounds; the inert gas is selected from one of nitrogen and carbon dioxide; the bacteriostatic agent is selected from at least one of parabens, organic acids and their salts, quaternary ammonium compounds, chlorhexidine acetate, alcohols, phenols and volatile oils; the local anesthetic is selected from at least one of benzyl alcohol, chlorobutanol, lidocaine and procaine; the pH regulator is selected from at least one of hydrochloric acid, sulfuric acid, phosphoric acid, citric acid, tartaric acid, acetic acid, sodium hydroxide, sodium bicarbonate, ethylenediamine, meglumine, phosphate, acetate and citrate; the isotonic or isosmotic regulator is selected from at least one of glucose, sodium chloride, sodium citrate, sorbitol and xylitol.

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