Effects of Tanshinone IIA on Calcium Overload and Pyroptosis in Radiation-induced Heart Disease Evaluated in Vivo and in Vitro

Radiation-induced heart disease (RIHD) has become an unavoidable and challenging problem that greatly impacts the outcomes of patients with tumors undergoing radiotherapy. Many studies have shown the positive effects of tanshinone IIA on cardiac function; however, its exact role and the underlying mechanism in RIHD remain unclear. This study aimed to investigate the mechanism of RIHD and examine the protective effects of tanshinone IIA. We developed in vitro and in vivo models of RIHD and assessed the damage caused by X-ray radiation to mice hearts and H9c2 cells using echocardiography, myocardial enzyme analysis, histopathology, transmission electron microscopy, Western blotting, and immunohistochemistry, to thoroughly explore the therapeutic potential and mechanism of tanshinone IIA on radiation-induced heart injury. Based on the results from various experiments, we confirmed that X-rays can trigger an increase in brain natriuretic peptide (BNP), creatine kinase-MB (CK-MB), and lactate dehydrogenase (LDH) levels, along with myocardial tissue edema, nuclear dissolution, and mitochondrial damage in mice. H9c2 cell activity declined, LDH levels rose, and mitochondrial damage occurred. Similarly, there was an increase in calcium ion flow, expression of calcium-related proteins, and pyroptosis-related proteins. After treatment with tanshinone IIA, the damage to the mouse heart and myocardial cells was partially reversed, with reductions in calcium ion flow and the expression of calcium- and pyroptosis-related proteins. These findings suggest that tanshinone IIA alleviates myocardial injury in RIHD by restoring calcium homeostasis and inhibiting pyroptosis.