c-Jun氨基末端激酶信号通路在大鼠脑缺血再灌注过程中的作用

目的探讨c-Jun氨基末端激酶(JNK)信号通路在大鼠脑缺血再灌注过程中所发挥的作用。方法雄性SD大鼠108只,体重290-310 g,随机分成假手术组(SH组)、缺血再灌注组(IR组)和JNK抑制剂SP600125组(SP组),分别于缺血前30 min侧脑室注射10 mL/L二甲基亚砜(DMSO)1、0 mL/L DMSO及JNK抑制剂SP600125。每组再根据再灌注时间分为2、6、12、24、487、2 h 6个亚组,每亚组6只动物。采用4-VO法建立SD大鼠全脑缺血模型,在预定时间点行灌注、固定、取脑、石蜡包埋切片;免疫组化方法检测p-JNK的表达变化,光镜下计数海马CA1区存活细胞,TUNEL法检测CA1区凋亡细胞。结果脑缺血再灌注后海马CA1区p-JNK在IR组有明显表达,于再灌注2 h时即明显升高,6 h时略有降低,后逐渐上升,24 h到高峰,之后表达量减小。SP组p-JNK的表达则无明显增高,各时点与IR组比较均有显著性差异(P<0.01)。海马CA1区神经元存活数目SP组明显高于IR组(P<0.01),凋亡指数显著低于IR组(P<0.01)。结论在大鼠全脑缺血再灌注损伤过程中,JNK信号通路发挥了重要作用,抑制JNK通路的激活可对脑缺血再灌注损伤导致的细胞损伤起到保护作用。

Effects of JNK signaling pathway on brain ischemia/reperfusion in rats

Objective To study the effects of the c-Jun N-terminal kinases(JNK) signaling pathway on brain ischemia/reperfusion in rats.Methods One hundred and eight SD rats weighing 290-310 g were randomly divided into 3 groups: the sham operation group(SH group),the ischemia/reperfusion group(IR group) and the JNK inhibitor SP600125 group(SP group).The rats in each group were given 1% DMSO,1% DMSO and SP600125,respectively,by ventricular infusion 30min right before the ischemia.Transient general brain ischemia(6 min) was induced by four-vessel occlusion,and the rats were perfusion-fixed at 2,6,12,24,48 and 72h after reperfusion.The brains were removed,embedded and sliced up.The p-JNK was detected by immunohistochemistry,and the number of surviving and apoptotic neurons detected by histochemistry and TUNEL in the hippocampal CA1 region was counted,respectively.Results The p-JNK in IR group was markedly expressed in the CA1 region,and reached the peak expression at 24 h after reperfusion.The level of p-JNK in SP group was much lower than that in IR group(P<0.01).In SP group,the number of surviving neurons in hippocampal CA1 region was much more than that in IR group(P<0.01),and the apoptotic index was much lower than that in IR group(P<0.01).Conclusion In the process of general brain ischemia/reperfusion injury,JNK signaling pathway plays an important role,and inhibition of JNK signaling pathway may help protect neurons against apoptosis.