Effects of isoflurane postconditioning on cerebral ischemia-reperfusion injury in rats

Abstract

Objective To evaluate the effects of isoflurane postconditioning on cerebral ischemia-reperfusion (I/R) injury in rats.Methods Thirty-two male Sprague-Dawley rats,weighing 280-320 g,were randomly divided into 4 groups (n=8 each):group sham operation (group S),group I/R,group isoflurane preconditioning (group Ⅰ-pre),and group isoflurane postconditioning (group Ⅰ-post).Global cerebral I/R was induced by 4-vessel occlusion method described by Pulsinelli.1.5％ isoflurane was inhaled for 2h before ischemia in group Ⅰ-pre.1.5％ isoflurane was inhaled for 30 min immediately after onset of reperfusion in group Ⅰ-post.Neurological function was assessed and scored at 24h of reperfusion.The rats were sacrificed at 72h of reperfusion and hippocampi were isolated for determination of neuronal apoptosis (by TUNEL),caspase-3 expression (by immuno-histochemistry),and phosphorylated c-Jun N-terminal kinase (p-JNK) protein expression (by using Western blot) in hippocampal tissues.Apoptotic rate was calculated.Results Compared with S group,the number of grid cross was decreased,twist time was prolonged,hanging time was shortened,apoptotic rate was increased,and the expression of caspase-3 and p-JNK protein was up-regulated in I/R,I-pre and Ⅰ-post groups (P ＜ 0.05).Compared in I/R group,the number of grid cross was increased,twist time was shortened,hanging time was prolonged,apoptotic rate was decreased,and the expression of caspase-3 and p-JNK protein was down-regulated in Ⅰ-pre and Ⅰ-post groups (P ＜ 0.05).Compared with I/R group,the number of grid cross was decreased,hanging time was shortened,apoptotic rate was increased,and the expression of caspase-3 was up-regulated (P ＜ 0.05),and no significant changes in the expression of p-JNK protein were found in Ⅰ-post group (P ＞ 0.05).Conclusion Isoflurane postconditioning can reduce cerebral I/R injury,the efficacy is weaker than that of preconditioning and the mechanism is related to activation of JNK signal transduction pathway and inhibition of neuronal apoptosis in hippocampus of rats. Key words: Isoflurane; Ischemic preconditioning; Brain; Reperfusion injury; Postconditioning