中文摘要：

目的研究细胞外信号调节激酶（extracellular signal-regulated kinase,ERK）抑制剂对大鼠全脑缺血再灌注后海马caspase-3表达的影响,以探讨ERK在全脑缺血再灌注损伤中的作用机制。方法健康雄性SD大鼠90只,随机分为三组：假手术组（sham,n=30）,缺血再灌注组（IR,n=30）,PD98059组（PD,n=30）,采用4-VO法建立全脑再灌注模型。分别于再灌注后2,6,12,24,48,72 h给予处死,标本行HE染色、免疫组化染色观察SD大鼠海马CA1区细胞形态、细胞凋亡计数及P-ERK和Caspase-3表达。结果 HE染色显示PD组损伤较IR组轻。免疫组化结果表明,PD组海马CA1区12-72 h P-ERK表达和各时间点Caspase-3表达均较IR组明显减少（P〈0.05）。TUNNEL染色显示,PD组各时间点凋亡指数显著小于IR组（P〈0.05）。结论 PD98059抑制全脑缺血再灌注后SD大鼠海马CA1区Caspase-3表达,减少了细胞凋亡。提示全脑缺血再灌注损伤中,ERK表达参与了损伤机制。

英文摘要：

Objective To investigate the effect of extracellular signal-regulated kinase（ERK） inhibitor on expression of Caspase-3 in hippocampus after global cerebral ischemia/reperfusion in SD rats,and to explore the role of ERK in global cerebral ischemia/reperfusion injury.Methods Ninety healthy male SD rats were randomized into 3 groups：sham group（n=30）,ischemia/reperfusion group（IR group,n=30） and PD98059 group（PD group,n=30）.Global cerebral ischemia/reperfusion model was established by 4-vessel occlusion method.HE staining,immunohistochemical staining and TUNEL staining of brain tissue section were performed after reperfusion for 2,6,12,24,48,72 h.Cellular morphology,apoptosis index and expression of ERK and Caspase-3 in CA1 of hippocampus were observed and detected after reperfusion for 2,6,12,24,48,72 h.Results Cellular damage in PD group was weaker than that in IR group by HE staining.Immunohistochemical results showed that the expression of P-ERK in CA1 of hippocampus in PD group was significantly lower than that in IR group at 12-72 h after reperfusion（P0.05）,and the expression of Caspase-3 in CA1 of hippocampus in PD group was also significantly lower than that in IR group at each time point.Apoptosis index in PD group was lower than that in IR group at each time point by TUNEL staining（P0.05）.Conclusion PD98059 could inhibit the expression of ERK and Caspase-3 in CA1 of hippocampus and decrease the apoptosis after global cerebral ischemia/reperfusion injury,which suggests that ERK may participate in the global cerebral ischemia/reperfusion injury.