Na+/Ca2+ exchanger mediates ischemia-reperfusion injury by activation of CaMKⅡ in isolated rat heart
10.11817/j.issn.1672-7347.2018.01.005
- VernacularTitle:钠钙交换体激活CaMKⅡ介导大鼠离体心脏缺血再灌注损伤
- Author:
Lingheng KONG
1
;
Fei LIANG
;
Yulong CHEN
;
Ming WEI
;
Na SUN
;
Juanxia ZHU
;
Xingli SU
Author Information
1. 西安医学院基础部基础医学研究所
- Keywords:
Na+/Ca2+ exchanger;
Ca2+/calmodulin-dependent protein kinase Ⅱ;
phospholamban;
cytochrome c;
lactate dehydrogenase;
myocardial injury
- From:
Journal of Central South University(Medical Sciences)
2018;43(1):28-34
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the role of Na+/Ca2+ exchanger (NCX) in myocardial ischemiareperfusion injury and the underlying mechanisms.Methods:Forty Sprague-Dawley rats were divided into 4 groups randomly:a control group,a KBR7943 group,an ischemia-reperfusion group (IR group),and an IR plus KB-R7943 group (KB-R7943+IR group).Isolated Sprague Dawley male rat hearts underwent Langendorffperfusion.The ratio of left ventricular developed pressure (LVDP),left ventricular end-diastolic pressure (LVEDP),the infarct size of myocardium,and the lactate dehydrogenase (LDH) activity in the coronary flow was determined.HE staining was used to assess the change of myocardial morphology.Western blot was used to determine the levels of cleaved caspase-3,cytochrome c and the phosphorylation of Ca2+/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) and the Thr17 site ofphospholamban.Results:Compared with the control group,IR group significantly induced an enlarged infarct size,reduction of the ratio of LVDP,up-regulation of cytochrome c,cleaved caspase-3,p-CaMKⅡ and p-phospholamban,and increased in the activity of LDH,the level of LVEDP (P＜0.01) and the disordered myocardial morphology.These effects were significantly attenuated in the presence of KB-R7943 treatment (10 μmol/L).Conclusion:NCX mediates myocardial ischemia-reperfusion-induced cell apoptosis and necrosis through activation of CaMKⅡ.
