Osthole down-regulates miR-30a and promotes autophagy to protect rats against myocardial ischemia/reperfusion injury

Background: This study aims to investigate the changes in miR-30a expression and myocardial autophagy following osthole treatment in a myocardial ischemia/reperfusion injury model. Methods: Thirty male Wistar rats (weighing 170 to 220 g, aged 8 weeks) were randomly divided into three groups as control (sham) group, ischemia/reperfusion (model) group, and ischemia/reperfusion + osthole post-treatment (osthole) group. Masson's trichrome staining was used to detect myocardial collagen changes. Apoptotic cardiomyocytes in the ischemic area were labeled in situ by terminal deoxynucleotidyl transferase-mediated dUTP (2'-deoxyuridine 5'-triphosphate) nick end labeling assay. Levels of autophagy markers light chain 3 beta (LC3 beta) and Beclin-1 in myocardial tissue were detected by western blotting. Expression of miR-30a was detected by quantitative reverse transcription-polymerase chain reaction. Results: Compared with the sham group, ischemia/reperfusion significantly increased collagen contents. Osthole significantly inhibited the ischemia/reperfusion-increased collagen contents. Osthole inhibited the ischemia/reperfusion-increased myocardial fibrosis, myocardial swelling, necrosis, and myocardial atrophy. Osthole also significantly inhibited the ischemia/reperfusion-increased apoptosis of myocardial cells. Moreover, the conversion of LC3 beta-I to LC3 beta-II and the Beclin-1 expression were significantly inhibited by ischemia/reperfusion. Osthole treatment significantly increased the conversion of LC3 beta-I to LC3 beta-II and Beclin-1 expression in ischemia/reperfusion rats. Finally, the expression of miR-30a was significantly increased in ischemia/reperfusion rats, while Osthole suppressed the expression of miR-30a. Conclusion: Osthole promoted autophagy, thereby alleviating myocardial ischemia/reperfusion injury. Osthole protects the myocardium during autophagy by down-regulating miR-30a expression.