Wang Gang, Cui Jie, Guo Yifeng, Wang Yueqiang, Kang Ling, Liu Libo
Department of Cardiology, Affiliated Hospital of Taishan Medical College.
Int Heart J. 2016 Jul 27;57(4):483-9. doi: 10.1536/ihj.16-091. Epub 2016 Jun 29.
This study aimed to investigate the effects and molecular mechanism of cyclosporin A (CsA) on cobalt chloride (CoCl2)-induced injury in H9c2 embryonic rat cardiac cells. The results showed that CsA could protect H9c2 cells against CoCl2-induced hypoxic injury. CsA effectively improved cell viability, and decreased LDH leakage, cell apoptosis, MDA concentration, and ROS generation, and increased SOD activity, GSH production, and CAT activity in a dosedependent manner. In addition, CsA treatment blocked the CoCl2-induced increases in ROS production and mitochondrial dysfunction, including a decrease in membrane potential, cytochrome c (cyto-c) release, Bax/Bcl-2 imbalance, as well as the ratios of cl-casp-9/casp-9 and cl-casp-3/casp-3 ratios, via the inhibition of p38 and ERK MAPK signaling pathways. The results also suggested that CsA protected H9c2 cells against CoCl2-induced hypoxic injury, possibly by suppressing the MAPK signaling pathway. Thus, CsA is a potential therapeutic agent for cardiac hypoxic injury.
本研究旨在探讨环孢素A（CsA）对氯化钴（CoCl2）诱导的H9c2胚胎大鼠心肌细胞损伤的影响及其分子机制。结果表明，CsA可保护H9c2细胞免受CoCl2诱导的缺氧损伤。CsA能有效提高细胞活力，剂量依赖性地降低乳酸脱氢酶（LDH）泄漏、细胞凋亡、丙二醛（MDA）浓度和活性氧（ROS）生成，并提高超氧化物歧化酶（SOD）活性、谷胱甘肽（GSH）生成和过氧化氢酶（CAT）活性。此外，CsA处理通过抑制p38和细胞外信号调节激酶（ERK）丝裂原活化蛋白激酶（MAPK）信号通路，阻断了CoCl2诱导的ROS生成增加和线粒体功能障碍，包括膜电位降低、细胞色素c（cyto-c）释放、Bax/Bcl-2失衡以及cl-casp-9/casp-9和cl-casp-3/casp-3比值升高。结果还提示，CsA可能通过抑制MAPK信号通路保护H9c2细胞免受CoCl2诱导的缺氧损伤。因此，CsA是一种潜在的治疗心脏缺氧损伤的药物。
