Role of Akt-GSK3β signaling pathway in long-term neuroprotection induced by propofol postconditioning in a rat model of focal cerebral ischemia/reperfusion injury
10.3760/cma.j.issn.0254-1416.2013.01.025
- VernacularTitle:Akt-GSK3β通路在丙泊酚后处理对脑缺血再灌注大鼠长时程脑保护效应中的作用
- Author:
Ying WEI
;
Guolin WANG
;
Haiyun WANG
;
Chenxu WANG
- Publication Type:Journal Article
- Keywords:
Protein-serine-threonine kinases;
Glycogen synthase kinase 3;
Propofol;
Reperfusion injury;
Brain
- From:
Chinese Journal of Anesthesiology
2013;(1):91-94
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the role of Akt-glycogen synthase kinase-3 beta (GSK3β) signaling pathway in the long-term neuroprotection induced by propofol postconditioning in a rat model of focal cerebral ischemia/reperfusion (I/R) injury.Methods Two hundred and sixteen male Sprague-Dawley rats,weighing 250-280 g,were randomly divided into 4 groups (n =54 each):sham operation group (group S),I/R group,intralipid control group (group I) and propofol postconditioning group (group P).The model of focal cerebral I/R injury was established by middle cerebral artery occlusion.Propofol 20 mg·kg-1 · h-1 was infused over 2 h starting from the onset of reperfusion in group P,the equal volume of normal saline was given in groups S and I/R and the equal volume of 10％ intralipid was given in group I.Six rats were chosen at 3,7,14 and 28 days after occlusion and sacrificed,and brains were removed for determination of the cerebral infarct size by TTC staining.Another 6 rats were chosen at 3,7,14 and 28 days after occlusion to detect the expression of Akt,GSK3β and phosphorylation of Akt and GSK3β by Western blot.The left 6 rats were chosen at 28 day after occlusion to measure the number of newly generated neurons in hippocampal dentate gyms on the ischemic side.Results Compared with group S,the cerebral infarct volume was significantly enlarged,the newly generated neurons number was increased in the other 3 groups,and the phosphorylation of Akt and GSK3β was decreased in groups I/R and I,while increased in group P (P ＜ 0.05).The cerebral infarct volume was significantly smaller,and the newly generated neurons number and phosphorylation of Akt and GSK3β were higher in group P than in group I/R (P ＜ 0.05).Conclusion The mechanism by which propofol postconditioning provides the long-term neuroprotection is related to Akt-GSK3β signaling pathway in a rat model of focal cerebral I/R injury.
