2024, 42(4):375-383.
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.