中药药理与临床2025，Vol.41Issue(3)：41-47,7.
养心定悸胶囊通过调控ROS-NLRP3-GSDMD通路抑制ISO诱导的缺血性心律失常的作用研究
Yangxin Dingji(养心定悸)Capsules Inhibit ISO-Induced Ischemic Arrhythmia by Regulating ROS-NLRP3-GSDMD Pathway
摘要
Abstract
Objective:To explore the mechanism of Yangxin Dingji(养心定悸)Capsules in protecting the myocardia in rats from ischemic arrhyth-mia based on the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)-mediated pyroptosis.Methods:Fifty SPF-grade male SD rats were randomly assigned into 5 groups(n=10):normal control,model control,propranolol(0.015 g/kg),and Yangxin Dingji Capsules(0.5 g/kg and 2 g/kg).The rat model of arrhythmia was established by"6+1"injection of isoproterenol.Rats in each group were administrated with corresponding drugs by gavage for 1 week.The electrocardiogram of rats was observed by a BL-420F system,and the ar-rhythmia score was recorded.The pathological changes of the myocardial tissue were observed by hematoxylin-eosin staining.The ultrastruc-tural changes of mitochondria in cardiomyocytes were examined by transmission electron microscopy.The serum levels of malondialdehyde(MDA),superoxide dismutase(SOD),and catalase(CAT)were measured by biochemical methods.The expression of reactive oxygen spe-cies(ROS)in the myocardial tissue was detected by the immunofluorescence assay.The mRNA levels of Nlrp3 and interleukin(IL)-18 in the myocardial tissue were determined by RT-qPCR.The protein levels of NLRP3,caspase-1,gasdermin D(GSDMD),N-terminal domain of GSDMD(GSDMD-NT),and IL-18 were determined by SP or Western blot.Results:Compared with the normal control group,the model con-trol group showed persistent arrhythmia,elevated MDA level and lowered SOD and CAT levels in the serum(P<0.01),unclear structure of cardiomyocytes and disarrangement of myocardial fibers,ruptured mitochondrial membrane,dissolved mitochondrial cristae,enhanced fluores-cence intensity of ROS in the myocardial tissue(P<0.01),and up-regulated mRNA and protein levels of Nlrp3,Caspase-1,Gsdmd and IL-18(P<0.01).Compared with the model control group,each treatment decreased the incidence of arrhythmia and the arrhythmia score(P<0.05 or P<0.01),lowered the levels of oxidative stress-related indicators(P<0.01),rearranged the myocardial cells and myocardial fibers,allevi-ated mitochondrial damage,decreased the expression of ROS(P<0.01),and down-regulated the expression of inflammation-and pyroptosis-related factors in the myocardial tissue(P<0.05 or P<0.01).Conclusion:Yangxin Dingji Capsules can regulate the expression of NLRP3 to inhibit the pyroptosis of cardiomyocytes,which may be an important mechanism of Yangxin Dingji Capsules in treating ischemic arrhythmia.关键词
养心定悸胶囊/心律失常/核苷酸结合寡聚化结构域样受体蛋白3炎症小体/线粒体/细胞焦亡Key words
Yangxin Dingji(养心定悸)Capsules/Arrhythmia/Nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)/Mitochondria/Pyroptosis引用本文复制引用
田雪,王海,杨婉悦,刘坤,冯亚萌,钱博璋,马国平,梁文杰..养心定悸胶囊通过调控ROS-NLRP3-GSDMD通路抑制ISO诱导的缺血性心律失常的作用研究[J].中药药理与临床,2025,41(3):41-47,7.基金项目
河北省中医药管理局项目(编号:2020149). （编号:2020149）
