The role of PI3K-Akt signal pathway in protection of myocardium agalnst ischemia-reperfusion injury by diazoxide postconditioning in rats
10.3760/cma.j.issn.0254-1416.2011.07.029
- VernacularTitle:PI3K-Akt信号通路在二氮嗪后处理减轻大鼠心肌缺血再灌注损伤中的作用
- Author:
Qihong ZHAO
;
Ying ZHANG
;
Hengfei LUAN
;
Yinming ZENG
;
Ying YE
;
Guoli GONG
- Publication Type:Journal Article
- Keywords:
1-Phosphafidylinositol 3-kinase;
Protein-serine-threonine kinases;
Diazoxide;
Myocardial reperfusion injury
- From:
Chinese Journal of Anesthesiology
2011;31(7):874-877
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the role of phosphatidylinositol 3-kinase/protein-serine-threonine kinases (PI3K-Akt) signal pathway in the protection of myocardium against ischemia-reperfusion (I/R) injury by diasoxide postconditioning in rats.MethodsThirty-six male SD rats weighing 250-300 g were randomly divided into 4 groups using random number table (n =9 each):group I/R; group diazoxide (group D); group wortmannin (PI3K inhibitor) (group W) and group wortmannin + diazoxide (group WD).The animals were anesthetized with intraperitoneal 10% chloral hydrate 4 ml/kg,intubated and mechanically ventilated.Myocardial I/R was produced by 30 min occlusion of left anterior descending coronary artery followed by 120 min reperfusion.0.1% dimethyl sulfoxide (the vehicle for diazoxide and wortmannin)/diazoxide at 0.47 mg· kg-1 · min-1/wortmannin at 1 μg·kg-1 ·min-1 was infused for 15 min starting from 25 min of ischemia in groups I/R,D and W respectively.In group DW wortmannin was infused at 5 min before diazoxide infusion.Blood samples were collected from left ventricle at the end of 120 min reperfusion for measurement of lactate dehydrogenase (LDH) activity.Myocardial infarct size was measured.Myocardial specimens were obtained for determination of apoptosis index (the number of apoptotic cells/the total number of cells examined) and expression of Bcl-2 and Bax.Bcl-2/Bax ratio was calculated.ResultsDiazoxide postconditioning significantly decreased plasma LDH activity,myocardial infarct size,apoptosis index and Bax expression in myocardium and increased myocardial Bcl-2 expression and Bcl-2/Bax ratio in group D compared with group I/R.Wortmannin partly counteracted the protective effects of diazoxide postconditioning against myocardial infarct.There was no significant difference in the above variables between groups I/R and W.ConclusionPI3K-Akt signal pathway is involved in the protective effects of diazoxide postconditioning on myocardium against I/R injury.