Background Myocardial ischemia-reperfusion (I/R) injury is a common clinical problem after myocardial infarction reperfusion. However, the mechanism of autophagy in myocardial I/R process is not fully understood.
Objective To investigate the mechanism of scutellarin in protecting myocardial ischemia reperfusion injury by promoting autophagy through the transcription factor cyclic adenylate response element binding protein (CREB).
Methods Corresponding research was carried out on the basis of 50 µmol/L Scu as the optimal response concentration. The experimental groups were divided into normal control (vehicle) group, ischemia-reperfusion injury (I/R) group, Scu intervention (Scu + I/R) group and CREB inhibition combined with Scu intervention (KG501 + Scu + I/R) group. The mouse-derived cardiomyocyte I/R model was established by glucose-oxygen deprivation culture, and MTT method was used to measure cell viability; biochemical method was used to measure SOD, MDA, LDH and ATP levels; RT-PCR was used to measure Opa1 and Drp1 expression; Western blots were used to measure LC3, CREB and p-CREB expression.
Results MTT assay found that compared with other concentrations, 50 µmol/L of scutellarin could significantly increase cell viability, resulting in the increase of SOD expression in I/R injured cardiomyocytes (P＜0.01), ATP production (P＜0.01) and LC3Ⅱ/Ⅰ ratio (P＜0.05), Opa1 (P＜0.01) mRNA expression and the p-CREB/CREB ratio, while the decrease of MDA expression (P＜0.01), LDH expression (P＜0.01), and Drp1 (P＜0.01) mRNA expression. CREB inhibitor (KG-501) could significantly reduce the expression of ATP and the ratio of p-CREB/CREB in the SCU treatment group (P＜0.01), and reduce the ratio of LC3Ⅱ/Ⅰ (P＜0.05).
Conclusion Scu can promote autophagy of ischemic cardiomyocytes, relieve oxidative damage, and improve the vitality of cardiomyocytes. In the process of protecting myocardial ischemia-reperfusion injury, Scu may regulate autophagy through the CREB pathway.
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