川芎嗪和缺血预适应对大鼠再灌注脑损伤的保护作用

Protective effect of tetramethylpyrazine and ischemic preconditioning against cerebral ischemic reperfusion injury in rats

目的探讨缺血预适应和川芎嗪对大鼠缺血再灌注脑损伤的保护效应,及其与ERK的关系。方法健康雄性SD大鼠40只,随机分为5组:对照组、缺血再灌注组、预适应+缺血再灌注组、川芎嗪+缺血再灌注组、预适应+川芎嗪+缺血再灌注组,采用预适应川芎嗪全脑缺血再灌注损伤动物模型,各组动物待观察到预定时间后,处死大鼠,进行HE常规染色观察大脑皮层的病理学改变,免疫组化SP法检测p-ERK的表达。结果①组织学检查显示预适应与川芎嗪均可使神经细胞缺血再灌注损伤改变减轻,而预适应联合川芎嗪使神经细胞缺血再灌注损伤显著减轻,细胞基本完好,未见明显损害。②缺血再灌注组p-ERK免疫反应阳性细胞数高于照组(P<0.01),预适应+缺血再灌注组、川芎嗪+缺血再灌注组、预适应+川芎嗪+缺血再灌注组p-ERK阳性表达细胞数均低于缺血再灌注组(P<0.01)。预适应+川芎嗪+缺血再灌注组p-ERK阳性表达数低于预适应+缺血再灌注组、川芎嗪+缺血再灌注组(P<0.01)。结论①预适应和川芎嗪干预均可减轻大鼠脑缺血再灌注损伤。②川芎嗪和预适应对脑保护有协同作用。③上述保护作用均与ERK有关。

Objective To explore the protective effect of ischemic preconditioning（IPC） and tetramethylpyrazine（TMP）against ischemic reperfusion （IR）injury in brain, and their relationship with extracellular signal-regulated kinase. Methods Forty healthy male SD rats were randomly assigned into 5 groups：control group,IR group,TMP ＋ IR group,IPC ＋ IR group,TMP ＋ IPC ＋ IR group. The IR injury model was established by tetramethylpyrazine and global brain ischemia reperfusion. The rats were executed at preset time. The pathological changes of cerebral cortex were observed by HE. The expression of p-ERK was detected by SP immunohistoehemistry. Results （1）Histopathological examination showed that the IR damages of cerebral cortex were lessened in TMP ＋ IR group and IPC ＋ IR group. The cerebral ischemic reperfusion injury significantly alleviated in TMP ＋ IPC ＋ IR group. （2）The p-ERK positive cell numbers in IR group were higher than in control group（P 〈0.01 ） ,and also higher than in IPC ＋ IR group,TMP ＋ IR group,TMP ＋ IPC ＋ IR group （P 〈0.01 ）. The p-ERK positive cell numbers in TMP ＋ IPC ＋ IR group were significantly lower than in IPC ＋ IR group and TMP ＋ IR group（ P 〈 0.01 ）. Conclusion （1）Ischemic preconditioning and tetramethylpyrazine can both alleviate cerebral ischemic reperfusion injury. （2）Tetramethylpyrazine and ischemic preconditioning have a synergetic protective effect on cerebral ischemic reperfusion injury. （3）Cerebral protective effect above-mentioned is related with ERK.