Role of c-Jun N-terminal kinase signaling pathway in isoflurane preconditioning against cerebral ischemia/reperfusion injury / 中华创伤杂志

ABSTRACT

Objective To evaluate the role of c-Jun N-terminal kinase (JNK) signaling pathway in isoflurane (ISO) preconditioning against cerebral ischemia/reperfusion (I/R) injury and investigate the relationship between JNK signaling pathway and apoptosis.Methods Global cerebral I/R models were made by 4-artery occlusion technique.Forty male SD rats of clean grade were divided into sham operation group (S group),I/R injury group (I/R group),SP600125 (an inhibitor of JNK signaling pathway) + I/R group (SP + I/R group),ISO preconditioning group (ISO group),and ISO preconditioning + SP600125 group (ISO + SP group) according to the random number table.Preconditioning protocol was successive inhalation of 15 g/L ISO for 5 days,1 h/d.I/R was induced at 24 hours after the end of preconditioning.Brain tissues were harvested at 72 hours later to take histomorphological examination by HE staining as well as detect apoptosis of hippocampal nerve cells by TUNEL method,expression of caspase-3 in hippocampal nerve cells by immuno-histochemistry,and expression of protein p-JNK in hippocampal tissues by Western blot.Results Compared with S group,brain injury score,apoptosis ratio of nerve cells,and expression of caspase-3 were significantly increased in the other groups (P ＜ 0.05).Moreover,p-JNK protein had a higher expression in IR group than in S group (P ＜ 0.05),but no significant difference was observed in SP + I/R group,ISO group,and ISO + SP group as compared with S group (P ＞ 0.05).Compared with I/R group,brain injury score,apoptosis ratio of nerve cells,expression of caspase-3,and expression of p-JNK protein were all declined in SP + I/R group,ISO group,and ISO + SP group (P ＜ 0.05).Moreover,brain injury score,apoptosis ratio of nerve cells,and expression of caspase-3 had further decline in ISO + SP group as compared with SP + I/R group and ISO group (P ＜ 0.05),but the difference in expression of p-JNK protein was insignificant among the three groups.Compared with SP + I/R group,no significant changes of each index were found in ISO group.Conclusion ISO preconditioning alleviates cerebral I/R injury through down-regulating expression of caspase-3 and inhibiting JNK signaling pathway.