肉桂酸减轻缺氧/复氧诱导的大鼠心肌细胞系损伤OA

Objective To explore the mechanism of cinnamic acid(CA)in improving anoxia/reoxygenation(A/R)-induced myocardial cell injury.Methods H9c2 cells were assigned into control group,A/R group,low-dose and high-dose groups of cinnamic acid,HIF-1α activator(DMOG)group,and high-dose cinnamic acid+HIF-1α inhibitor(IDF-11774)group.Cell viability was assessed using the CCK-8 assay.Levels of lac-tate dehydrogenase(LDH)and creatine kinase-MB(CK-MB)in the supernatant were measured by ELISA.Mitochondrial ultrastructure was observed via transmission electron microscopy.Intracellular reactive oxygen species(ROS)and ferrous iron(Fe2+)levels were detected using 2′,7′-dichlorodihydrofluorescein diacetate(DCFH-DA)and FerroOrange fluorescent probes,respectively.Malondialdehyde(MDA)levels and superox-ide dismutase(SOD)activity were determined using commercial kits.Protein expression of HIF-1α,SLC7A11,and GPX4 was analyzed by Western blot.Results Compared with the control group,the A/R group exhibited mitochondrial atrophy,severe cristae disruption,and partial outer membrane rupture.Addi-tionally,cell viability and SOD activity,along with HIF-1α,SLC7A11,and GPX4 protein levels,were sig-nificantly decreased,whereas LDH and CK-MB release,ROS production,MDA levels,and Fe2+accumulation were significantly increased(P<0.05).Compared with the A/R group,the low and high-dose cinnamic acid groups,and DMOG group showed reduced mitochondrial structural injury in H9c2 cells,raised cell viability,SOD activity,HIF-1α,SLC7A11,and GPX4 proteins,and decreased cell supernatant LDH,CK-MB levels,cell ROS fluorescence intensity,MDA and Fe2+fluorescence intensity(P<0.05).IDF-11774 attenuated the inhibitory effect of high-dose cinnamic acid on A/R induced ferroptosis in H9c2 cells and its im-provement effect on cell injury.Conclusions Cinnamic acid alleviates A/R-induced cardiomyocyte injury by inhibiting ferroptosis,likely through activation of the HIF-1α/SLC7A11/GPX4 signaling pathway.