Role of Akt/GSK-3β signaling pathway in isoflurane preconditioning-induced inhibition of mPTP opening during myocardial ischemia-reperfusion in rats
10.3760/cma.j.issn.0254-1416.2016.07.011
- VernacularTitle:Akt/GSK-3β信号通路在异氟醚预处理抑制大鼠心肌缺血再灌注时mPTP开放中的作用
- Author:
Liuhui CHANG
;
Hong XIE
;
Xiaoxiao ZHANG
;
Xiaoming CHAI
;
Jiang ZHU
- Publication Type:Journal Article
- Keywords:
Isoflurane;
Ischemic preconditioning;
Myocardial reperfusion injury;
Mitochondrial membrane transport proteins;
Protein-serine-threonine kinases;
Glycogen synthase kinase 3
- From:
Chinese Journal of Anesthesiology
2016;36(7):814-818
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the role of serine-threonine kinase (Akt)/glycogen synthase kinase-3 beta (GSK-3β) signaling pathway in isoflurane preconditioning-induced inhibition of mitochondrial permeability transition pore protein (mPTP) opening during myocardial ischemia-reperfusion (I/R) in rats.Methods Ninety-six male Sprague-Dawley rats,aged 3-4 months,weighing 200-250 g,were randomly divided into 4 groups (n =24 each) using a random number table:control group (group C);I/R group;isoflurane preconditioning group (group IPC);Akt inhibitor MK-2206 group (group MK).Myocardial I/R was induced by occlusion of the anterior descending branch of the left coronary artery for 30 min followed by 2 h of reperfusion.In group IPC,1.5％ isoflurane was inhaled for 30 min followed by 45 min washout,and then the model of myocardial I/R injury was established.In group MK,MK-2206 300 μg/kg (in dimethyl sulfoxide) was injected intraperitoneally at 30 min before isoflurane inhalation.At 2 h of reperfusion,8 rats were selected and sacrificed,and the hearts were removed for determination of myocardial infarct size.At 2 h of reperfusion,8 rats were selected,and blood samples were collected from the right internal jugular vein for determination of serum cardiac troponin Ⅰ (cTnI) concentrations.The rats were then sacrificed,and myocardial specimens were obtained for determination of the expression of phosphorylated GSK-3β (p-GSK-3β) in cytoplasm and mitochondria (by Western blot) and co-expression of p-GSK-3β with adenine nucleotide translocator (ANT),voltage-dependent anion channel or cyclophilin D in myocardial tissues (using co-immunoprecipitation).At 2 h of reperfusion,8 rats were selected and sacrificed,myocardial cells were obtained,and the opening time of mPTP was determined with a laser scanning confocal microscope.Results Compared with group C,the myocardial infarct size and serum cTnI concentrations were significantly increased,and the expression of p-GSK-3β in cytoplasm and mitochondria was up-regulated in I/R and IPC groups,the co-expression of p-GSK-3β with ANT was significantly down-regulated,and the opening time of mPTP was shortened in group I/R,and the co-expression of p-GSK-3β with ANT was significantly up-regulated,and the opening time of mPTP was prolonged in group IPC (P＜0.05).Compared with group I/R,the myocardial infarct size and serum cTnI concentrations were significantly decreased,the expression of p-GSK-3β in cytoplasm and mitochondria was up-regulated,the co-expression of p-GSK-3β with ANT was significantly up-regulated,and the opening time of mPTP was prolonged in group IPC,and the opening time of mPTP was significantly prolonged (P＜0.05),and no significant change was found in the other parameters in group MK (P＞0.05).Compared with group IPC,the myocardial infarct size and serum cTnI concentrations were significantly increased,the expression of p-GSK-3β in cytoplasm and mitochondria was up-regulated,the co-expression of p-GSK-3β with ANT was significantly down-regulated,and the opening time of mPTP was shortened in group MK (P＜0.05).No co-expression of p-GSK-3β with voltage-dependent anion channel or cyclophilin D was found in myocardial tissues.Conclusion The mechanism by which isoflurane preconditioning inhibits mPTP opening during myocardial ischemia-reperfusion is partially related to activation of Akt/GSK-3β signaling pathway in rats.
