Dihydromyricin alleviates doxorubicin-induced myocardial injury by inhibiting NLRP3 inflammasome in rats

Abstract

Objective: To investigate the protective effect of dihydromyricetin (DHM) on doxorubicin (DOX)-induced myocardial injury and its mechanism. Methods: Twenty-four healthy male SD rats were divided into 4 groups: control group, DOX group, DOX+DHM100 group and DOX+DHM200 group. Echocardiography was used to measure cardiac function. At the end of the 6th week, the rats were anesthetized and sacrificed, and the pathological changes of the cardiac tissues were observed by HE staining, Masson staining and WGA staining. Cardiomyocyte apoptosis was observed by TUNEL staining, and protein levels of NLRP3, caspase-1, IL-1β, bax and bcl-2 were detected by Western blot and immunohistochemistry. Results: Compared with the control group, the left ventricular ejection fraction and left ventricular fractional shortening decreased significantly in DOX group, while left ventricular internal dimension at systole and left ventricular internal dimension at diastole increased. In DOX+DHM group, both left ventricular ejection fraction and left ventricular fractional shortening increased, while left ventricular internal dimension at systole and left ventricular internal dimension at diastole decreased (P<0.05). Furthermore, DOX group showed significant myocardial injury histologically, while DOX+DHM group significantly inhibited DOX-induced myocardial injury in rats. Meanwhile, cardiomyocyte hypertrophy was found in the DOX group, while the cardiomyocyte hypertrophy was notably inhibited in the DOX+DHM group. Compared with the control group, the apoptotic rates of cardiomyocytes and the levels of bax/bcl-2 ratio were significantly increased in DOX group, which were significantly alleviated in the DOX+DHM group (P<0.05). In addition, the levels of NLRP3, caspase-1 and IL-1β were increased as compared with control group, while the levels of the above indicators were remarkably reversed in DOX+DHM group as compared with DOX group (P<0.05). Conclusion: DHM alleviates DOX-induced myocardial injury in rats by inhibiting NLRP3 inflammasome and reducing cardiomyocyte apoptosis.