南方医科大学学报2018，Vol.38Issue(2)：181-186,6.DOI:10.3969/j.issn.1673-4254.2018.02.10
抑制CaMKII减轻线粒体氧化应激可改善离体心脏缺血再灌注损伤
Inhibition of CaMKII alleviates myocardial ischemia-reperfusion injury by reducing mitochondrial oxidative stress in isolated perfused rat heart
摘要
Abstract
Objective To investigate the role of calcium/calmodulin-dependent protein kinase Ⅱ (CaMKII) in myocardial ischemia-reperfusion (IR) injury in isolated perfused rat heart and explore the underlying mechanisms. Methods An ischemia-reperfusion (IR) model was prepared using isolated rat hearts perfused with Krebs-Henseleit solution were randomly divided into control group, 2.5μmol/L KN-93 group, IR (induced by ischemia for 45 min followed by reperfusion for 120 min) group and KN-93+IR group. The myocardial performance was evaluated by assessing the left ventricular pressure. Lactate dehydrogenase (LDH) activity and cTnI content in the coronary flow and the infarct size were determined to evaluate the myocardial injury. The phosphorylation of CaMKII (p-CaMKII) and PLN (p-PLN) and oxidation of CaMKII (ox-CaMKII) were measured with Western blotting. The activity of mitochondrial superoxide dismutase (SOD) and the content of malondialdehyde (MDA) were determined using ELISA. Results Compared with the control group, KN-93 treatment at 2.5 μmol/L produced no significant effects on cardiac function or performance in rat hearts without IR injury. Myocardial IR injury significantly decreased myocardial performance and mitochondrial SOD activity in the perfused hearts (P<0.01) and caused significantly increased infarct size, LDH activity, cTnI content, expressions of p-CaMKII, ox-CaMKII and p-PLN, and also increased mitochondrial MDA content (P<0.01). KN-93 treatment at 2.5μmol/L administered before ischemia and before reperfusion markedly attenuated such changes induced by ischemia and reperfusion (P<0.01). Conclusion CaMKII participates in myocardial IR injury in isolated rat heart, and inhibiting CaMKII can alleviate myocardial injury by relieving mitochondrial oxidation stress.关键词
钙/钙调蛋白依赖的蛋白激酶Ⅱ/心脏缺血再灌注损伤/线粒体/超氧化物歧化酶/丙二醛Key words
calcium/calmodulin-dependent protein kinase Ⅱ/myocardial ischemia reperfusion injury/mitochondria/superoxide dismutase/malondialdehyde引用本文复制引用
孔令恒,陈玉龙,孙娜,魏明,朱娟霞,苏兴利..抑制CaMKII减轻线粒体氧化应激可改善离体心脏缺血再灌注损伤[J].南方医科大学学报,2018,38(2):181-186,6.基金项目
陕西省教育厅重点实验室科研计划项目(16JS098) （16JS098）
陕西省缺血性心血管疾病重点实验室开放基金(2017ZDKF10) （2017ZDKF10）
陕西省基础医学优势学科建设经费(陕教位[2014]3号-1001) （陕教位[2014]3号-1001）
陕西省中医管理局中医药基础研究项目(JCMS023) （JCMS023）
西安医学院校级重点学科(神经-内分泌生理) （神经-内分泌生理）
