中国药房2025，Vol.36Issue(18)：2267-2272,6.DOI:10.6039/j.issn.1001-0408.2025.18.09
茯苓酸通过调控PINK1/Parkin信号通路介导的线粒体自噬改善冠心病大鼠心肌损伤
Improvement effects of pachymic acid on myocardial injury in coronary heart disease rats by regulating mitochondrial autophagy mediated by the PINK1/Parkin signaling pathway
摘要
Abstract
OBJECTIVE To explore whether pachymic acid(Pac)regulates mitochondrial autophagy mediated by the PTEN-induced kinase 1(PINK1)/Parkin RBR E3 ubiquitin-protein ligase(Parkin)signaling pathway to alleviate myocardial injury in coronary heart disease(CHD)rats.METHODS SD rats were divided into control(Con)group,CHD group,Pac low-dose group(Pac-L group),Pac high-dose group(Pac-H group),Pac-H+PINK1/Parkin signaling pathway inhibitor group(Pac-H+3-MA group),with 10 rats in each group.Except for the Con group,CHD models were established in the remaining groups of rats.After successful modeling,the rats in each group were intraperitoneally injected with the corresponding drugs or normal saline.After continuous intervention for 4 weeks,the left ventricular ejection fraction(LVEF),left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV),and mean arterial pressure(MAP)of the rats were detected.The levels of creatine kinase isoenzyme(CK-MB),lactate dehydrogenase(LDH),cardiac troponin I(cTnI),and cardiac troponin T(cTnT)in the serum,as well as the levels of tumor necrosis factor-α(TNF-α),interleukin-10(IL-10),IL-1β,reactive oxygen species(ROS),malondialdehyde(MDA)in the myocardial tissue,and the activities of catalase(CAT)and superoxide dismutase(SOD),as well as the expression levels of p62,cleaved caspase-3,Parkin,PINK1 proteins and the ratio of microtubule-associated protein 1 light chain 3 Ⅱ(LC3Ⅱ)/LC3Ⅰ ratio were measured.The morphology of myocardial tissue and mitochondrial autophagic vesicles were observed,and the number of mitochondrial autophagic vesicles per unit area and the rate of cardiomyocyte apoptosis were counted.RESULTS Compared with CHD group,LVEF,MAP,IL-10 levels,CAT and SOD activities,p62,Parkin,PINK1 protein expressions,LC3Ⅱ/LC3Ⅰ ratio,the numbers of mitochondrial autophagic vesicles per unit area in the Pac-L and Pac-H groups were increased significantly(P＜0.05);the levels of LVEDV,LVESV,CK-MB,LDH,cTnI,cTnT,TNF-α,IL-1β,ROS and MDA,cell apoptosis rates,and protein expression of cleaved caspase-3 were all decreased significantly(P＜0.05);and the changes in various indicators were more pronounced in the Pac-H group(P＜0.05);both groups showed varying degree of improvement in myocardial histopathological morphology.Compared with the Pac-H group,the aforementioned indicators in rats from the Pac-H+3-MA group were all significantly reversed(P＜0.05).CONCLUSIONS Pac may promote mitochondrial autophagy in cardiomyocytes of CHD rats by activating the PINK1/Parkin signaling pathway,thereby reducing inflammatory responses and oxidative stress and improving myocardial injury.关键词
茯苓酸/PINK1/Parkin信号通路/冠心病/心肌细胞/线粒体自噬Key words
pachymic acid/PINK1/Parkin signaling pathway/coronary heart disease/cardiomyocytes/mitochondrial autophagy分类
医药卫生引用本文复制引用
谢建,高波,梁珊珊,杨清,郭思言,龚龙家..茯苓酸通过调控PINK1/Parkin信号通路介导的线粒体自噬改善冠心病大鼠心肌损伤[J].中国药房,2025,36(18):2267-2272,6.基金项目
湖北省自然科学基金项目(No.2023AFC049) （No.2023AFC049）
