Tanshinone‑IIA inhibits myocardial infarct via decreasing of the mitochondrial apoptotic signaling pathway in myocardiocytes.

Myocardial ischemia triggers an inflammatory reaction and oxidative stress that increases apoptosis of myocardiocytes. It has been evidenced that tanshinone‑IIA (Tan‑IIA) protects against heart failure post‑myocardial infarction via inhibition of the apoptotic pathway. The purpose of the present study was to investigate the therapeutic effect of Tan‑IIA in a rat model of myocardial ischemia, and explore the possible mechanism of Tan‑IIA in myocardiocytes. The rat model of myocardial ischemia was established by left anterior descending coronary artery and rats received treatment with either Tan‑IIA (10 mg/kg) or PBS for 20 days continuously. The cardiac function in the experimental rat model was detected using the Sequoia 512 echocardiography system on day 21. The cell viability of myocardiocytes was assessed by CCK‑8 assay. Apoptosis of myocardiocytes and myocardial tissue was evaluated by TUNEL assay. The infarct size of the myocardial ischemia rat was determined through 2,3,5‑triphenyltetrazolium chloride (TTC) and Evan blue double staining assay. The expression levels of apoptotic factors were assessed by immunohistochemistry, western blotting and immunofluorescence. The results demonstrated that Tan‑IIA reduced myocardial infarct size and improved the myocardial function in myocardial ischemia rats. Compared with PBS, Tan‑IIA treatment decreased myocardial tissue apoptosis and the expression levels of caspase‑3, Cyto c and Apaf‑1 in myocardial tissue. Tan‑IIA increased the viability of impaired myocardiocytes, inhibited apoptosis of impaired myocardiocytes and increased Bcl‑2 and Bak expression in myocardiocytes. In addition, Tan‑IIA increased Bim and CHOP, decreased TBARS, ROS and H2O2 production, decreased ATF4 and IRE1α expression, and reduced intracellular calcium and oxidative stress in myocardiocytes. Furthermore, caspase‑3 overexpression blocked Tan‑IIA‑decreased apoptosis of myocardiocytes. In conclusion, the data in the present study indicated that Tan‑IIA improved myocardial infarct and apoptosis via the endoplasmic reticulum stress‑dependent pathway and mitochondrial apoptotic signaling pathway.