Cao Yuanyuan, Chen Zhangwei, Jia Jianguo, Chen Ao, Gao Yanhua, Qian Juying, Ge Junbo
Department of Cardiology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China.
Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Cardiovasc Toxicol. 2022 Apr;22(4):341-351. doi: 10.1007/s12012-021-09716-4. Epub 2022 Jan 7.
To explore the mechanism by which rosuvastatin prevents coronary microembolism (CME)-induced cardiac injury and cardiomyocyte apoptosis. Animal and cell models of CME were established and treated with different doses of rosuvastatin. Echocardiography and histological staining were applied to assess left ventricular function and cardiac injury. Masson trichrome staining was used to evaluate fibrin deposition in the myocardium. The activity of lactate dehydrogenase (LDH) in serum and cell culture supernatant was detected. TUNEL staining and flow cytometry were used to evaluate apoptosis in myocardium and cardiomyocytes, respectively. The activity of ROS was revealed by DHE staining. The expression levels of Nox2, cleaved caspase-3, cytochrome C, p53, Bax and Bcl-2 were also detected. Rosuvastatin pretreatment improved the left ventricular function of CME mice and reduced inflammatory cell infiltration and fibrin deposition in the myocardium. Rosuvastatin reduced the production of ROS by inhibiting the expression of Nox2. Rosuvastatin also downregulated pro-apoptotic proteins cleaved caspase-3, cytochrome C, p53 and Bax, and upregulated anti-apoptotic Bcl-2. Rosuvastatin mitigates CME-induced cardiac injury by inhibiting Nox2-induced ROS overproduction and alleviating p53/Bax/Bcl-2-dependent cardiomyocyte apoptosis.
探讨瑞舒伐他汀预防冠状动脉微栓塞（CME）所致心脏损伤和心肌细胞凋亡的机制。建立CME动物和细胞模型，并用不同剂量的瑞舒伐他汀进行处理。应用超声心动图和组织学染色评估左心室功能和心脏损伤。采用Masson三色染色评估心肌中的纤维蛋白沉积。检测血清和细胞培养上清液中乳酸脱氢酶（LDH）的活性。分别用TUNEL染色和流式细胞术评估心肌和心肌细胞中的凋亡情况。通过DHE染色揭示活性氧（ROS）的活性。还检测了Nox2、裂解的半胱天冬酶-3、细胞色素C、p53、Bax和Bcl-2的表达水平。瑞舒伐他汀预处理改善了CME小鼠的左心室功能，减少了心肌中的炎性细胞浸润和纤维蛋白沉积。瑞舒伐他汀通过抑制Nox2的表达减少了ROS的产生。瑞舒伐他汀还下调了促凋亡蛋白裂解的半胱天冬酶-3、细胞色素C、p53和Bax，并上调了抗凋亡蛋白Bcl-2。瑞舒伐他汀通过抑制Nox2诱导的ROS过度产生和减轻p53/Bax/Bcl-2依赖性心肌细胞凋亡来减轻CME诱导的心脏损伤。
