Effect of local mild hypothermia on expression of PTEN protein during global cerebral ischemia-reperfusion in rats

Objective To evaluate the effect of local mild hypothermia on the expression of phosphatase and tensin homolog deleted on chromo-some ten (PTEN) protein during global cerebral ischemia-reperfusion (I/R) in rats.Methods One hundred and eight healthy adult male Wistar rats,weighing 230-280 g,were randomly divided into 3 groups (n =36 each) using a random number table:sham operation group (group S),cerebral I/R group (group I/R) and mild hypothermia cerebral I/R group (group HI/R).Global cerebral I/R was induced by 4-vessel occlusion method described by Pulsinelli.Bilateral vertebral arteries were permanently occluded by cauterization,and bilateral carotid arteries were occluded for 15 min.Nasopharyngeal cooling was applied and the nasopharyngeal temperature was reduced to 32.5-33.5 ℃ and maintained at this level for 1 h.When the nasopharyngeal temperature was reduced to 32.5-33.5 ℃,the bilateral carotid arteries were clamped in group HI/ R.Six rats were chosen to be anesthetized and sacrificed immediately before ischemia and at 4,8,12,24 and 72 h of reperfusion.Hippocampal specimens were obtained to detect the expression of phosphorylated PTEN (pPTEN),Bcl-2 and Bax protein (by immunohistochemistry) in hippocampal CA1 region,contents of S100B protein (by ELISA) and MDA (by thiobarbituric acid method),and activity of SOD (by xanthine oxidase method).Results Compared with group S,the expression of p-PTEN and Bcl-2 protein,ratio of Bcl-2/Bax protein and activity of SOD were significantly decreased,and the expression of Bax protein and contents of MDA and S100B protein were increased after reperfusion in group I/R (P ＜ 0.05),and the ratio of Bcl-2/Bax protein was decreased,and there was no significant difference in the expression of p-PTEN,Bcl-2 and Bax protein,activity of SOD and contents of MDA and S100B protein after reperfusion in group HI/R (P ＞ 0.05).Compared with group I/R,the expression of p-PTEN and Bcl-2 protein,Bcl-2/Bax ratio and activity of SOD were significantly increased and the expression of Bax protein and content of MDA and S100B protein were decreased after reperfusion in group HI/R (P ＜ 0.05).Conclusion The mechanism by which local mild hypothermia reduces cerebral damage is related to inhibition of activation of PTEN protein in the brain tissues during global cerebral I/R in rats. Key words: Hypothermia,induced;  Reperfusion injury;  Brain;  PTEN phosphohydrolase