Salidroside protects coronary endothelial cells against ischemia-reperfusion injury by regulating mitophagy

LIANG Zheng; HUANG Yao-ying; WEN Wen; ZHONG Jian-feng; MO Shao-men; HOU Gao-xing; LI Ming-liang

doi:10.3969/j.issn.1005-4057.2024.04.007

Abstract：Objective To investigate the modulation of salidroside(Sal)on mitophagy in coronary endothelial cells(CoECs)after myocardial infarction.Methods CoECs were divided into normal control,negative control(PBS),Sal,and Sal+Chloroquine(Sal+CQ)groups;Control group was treated with normoxic condition,while the other groups with oxygen/glucose deprivation and reperfusion(OGD/R).Cell viability,apoptosis,mitochondrial-lysosomal colocalization(MLCL),mitochondrial membrane potential(MMP),ROS,and autophagy-related protein levels were detected using CCK-8,fluorescent probe,and Western blot.Eighteen C57/BL6 mice were randomized to Sham,ischemia-reperfusion(MIRI),and MIRI+Sal groups.MIRI or MIRI+Sal group was intraperitoneally injected with normal saline or 50 mg/(kg·d)Sal 28 days before and after LAD ligation.Ejection fraction(EF),left ventricular fractional shortening(FS),myocardial fibrosis,and expression of autophagy-related proteins in infarcted coronary arteries were determined by small animal ultrasound imaging system,Masson stain and Western blot.Results Compared with PBS group,cell viability,MMP,MLCL,and expression of PINK1,Beclin1,and Parkin were increased(P<0.05),while apoptosis,ROS content,and expression of Mtfr1,P62,and LC3 Ⅱ/Ⅰ decreased in Sal Group(P<0.05).Compared with Sal group,cell viability,MLCL and expression of PINK1,Beclin1,and Parkin were reduced(P<0.05),while apoptosis,ROS content and expression of Mtfr1,P62,and LC3 Ⅱ/Ⅰ elevated(P<0.05)in Sal+CQ group.Compared with MIRI group,FS,EF and expression of PINK1,Parkin and Beclin1 were increased in infarcted coronary arteries,while myocardial fibrosis and expression of Mtfr1,P62/SQSTM1 and LC3 Ⅱ/Ⅰ decreased(P<0.05)in Sal+MIRI group.Conclusion Sal is protective for OGD/R-induced CoECs and infarcted coronary arteries in MIRI mice by inhibiting oxidative stress and promoting mitophagy.