Role of mitochondrial ATP-sensitive potassium channel in mitigation of cerebral ischemia-reperfusion injury by isoflurane preconditioning in rats: the relationship with JNK signaling pathway / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of mitochondrial ATP-sensitive potassium (mitoKATP) channel in mitigation of cerebral ischemia-reperfusion (I/R) injury by isoflurane preconditioning in rats and the relationship with c-Jun N-terminal kinase (JNK) signaling pathway.Methods Thirty-two male Sprague-Dawley rats,weighing 280-320 g,were randomly divided into 4 groups (n =8 each) using a random number tablesham operation group (group S),group I/R,isoflurane preconditioning group (group Ⅰ-pre),and 5-hydroxydecanoate (5-HD,a selective mitoKATP channel antagonist) group.Cerebral I/R was produced by modified 4-vessel technique described by Pulsinelli in anesthetized rats.In group Ⅰ-pre,the rats were exposed to 1.5％ isoflurane for 1 h everyday for 5 consecutive days before ischemia.In group 5-HD,5-HD 15 mg/kg was injected intraperitoneally at 30 min before ischemia and the other procedures were similar to those previously described in group Ⅰ-pre.Neurological behavior was evaluated at 24 h of reperfusion.The rats in each group were sacrificed at 72 h of reperfusion,and the brains were removed for determination of neuronal apoptosis (by TUNEL) and expression of caspase-3 and phosphor-JNK (p-JNK) protein (using Western blot) in hippocampal tissues.Apoptotic rate was calculated.Results Compared with group S,the number of grid cross was significantly decreased,hanging time was shortened,apoptotic rate was increased,and caspase-3 expression was up-regulated in I/R,Ⅰ-pre and 5-HD groups,the expression of p-JNK protein was up-regulated in IR and 5-HD groups,and no significant change was found in the expression of p-JNK protein in group Ⅰ-pre.Compare with group I/R,the number of grid cross was significantly increased,hanging time was prolonged,apoptotic rate was decreased,and the expression of caspase-3 and p-JNK protein was downregulated in group Ⅰ-pre,and no significant change was found in the parameters mentioned above in group 5-HD.Compared with group Ⅰ-pre,the number of grid cross was significantly decreased,hanging time was shortened,apoptotic rate was increased,and the expression of caspase-3 and p-JNK protein was up-regulated in group 5-HD.Conclusion The mitoKATP channel is involved in mitigation of cerebral I/R injury by isoflurane preconditioning through blocking the JNK signaling pathway in rats.