The Effect of Astragalus Polysaccharide on Pyroptosis of Myocardial Cells in Type 2 Diabetic Rats via the ASIC1/CaMKⅡ Pathway
LI Zhenzhen
HU Wenjing
PEI Hua
SUN Ran
ZHAO Nawei
WANG Chen
Abstract：Objective:To explore the effects of astragalus polysaccharides on the acid-sensitive ion channel 1(ASIC1)/calcium ion-calmodulin-dependent kinase Ⅱ(CaMKⅡ)pathway and cardiomyocyte pyroptosis in type 2 diabetic(T2DM)rats'myocardial tissues.Methods:Thirty SPF-grade male SD rats were randomly divided into the control group,the T2DM group,and the astragalus polysaccharide group,with 10 rats in each group.After the rats in the T2DM group and the astragalus polysaccharide group were fed high-fat and high-sugar diet for 4 weeks,streptozotocin(STZ)(35 mg/kg)was injected intraperitoneally.If the random fasting blood glucose(FPG)was>16.7 mmol/L 72 hours later,it indicated that the model was successfully established.The rats in the astragalus polysaccharide group continued to receive intragastric administration of astragalus polysaccharides(400 mg/kg)for 8 weeks.The control group was fed with regular feed.Blood glucose meter was used to detect FPG in rats.The kits was used to detect the levels of total cholesterol(TC),triglycerides(TG),interleukin(IL)-1β,and IL-18 in serum.Echocardiography was used to measure the left ventricular ejection fraction(LVEF),left ventricular short-axis shortening rate(LVFS),left ventricular diastolic end diameter(LVEDD),and the ratio of peak diastolic early velocity(E)to peak diastolic late velocity(A)of the mitral valve.The pathological morphology of rat myocardial tissue was examined using hematoxylin-eosin(HE)staining.Masson staining was used to detect the collagen deposition in the rat myocardial tissue.The protein immunoblotting method(Western Blot)was used to detect the protein levels of ASIC1,CaMKⅡ,NOD-like receptor protein 3(NLRP3)antibody,apoptosis-associated speck-like protein(ASC),and Cysteine protease(Caspase)-1 protein.The mRNA levels of ASIC1,CaMKⅡ,NLRP3,ASC and Caspase-1 were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).Results:Compared with the control group,the levels of FPG,TC,TG,IL-1β,and IL-18 in the T2DM group of rats increased(P<0.05).Compared with the T2DM group,the levels of FPG,TC,TG,IL-1β,and IL-18 in the astragalus polysaccharide group of rats decreased(P<0.05).Compared with the control group,the LVEF,E/A,and LVFS of the T2DM group rats decreased,while LVEDD increased(P<0.05).Compared with the T2DM group,the LVEF,E/A,LVFS in the astragalus polysaccharide group increased,and LVEDD decreased(P<0.05).Compared with the control group,the myocardial fibers disordered and broken in the T2DM group rats,and a large amount of collagen was deposited in the myocardial interstitium.Compared with the T2DM group,the rats in the astragalus polysaccharide group showed improvement of myocardial fiber damage and decrease of collagen deposition in the myocardial interstitium.Compared with the control group,the protein and mRNA expressions of ASIC1,CaMKⅡ,NLRP3,ASC,and Caspase-1 in the myocardial tissues of the T2DM group rats increased(P<0.05).Compared with the T2DM group,the expression levels of ASIC1,CaMKⅡ,NLRP3,ASC,and Caspase-1 proteins and mRNAs in the myocardial tissues of rats decreased in the astragalus polysaccharide group(P<0.05).Conclusion:Astragalus polysaccharides can improve the cardiac function and myocardial tissue pathological damage in T2DM rats,down-regulate the ASIC1/CaMKⅡ pathway,and inhibit cardiomyocyte pyroptosis.
Keywords：type 2 diabetes mellitusacid-sensitive ion channel 1/calcium ion-calmodulin-dependent kinase Ⅱ pathwayASIC1/CaMKⅡpathwayastragalus polysaccharidepyroptosis
Publication Date：2026-03-10
Online Publishing Date：2026-03-24(First online date of this platform, not the publication date of the document)
Pages：6( 678-683 )