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目的 研究双苯氟嗪抗大鼠全脑缺血再灌注损伤的作用机制。方法 大鼠全脑缺血 15min再灌注 3d,再灌注开始后给予双苯氟嗪 ( 20, 40和 80mg·kg-1,ig)。免疫组织化学方法观察Fas及Fas配体的分子定位,Westernblotting和RT PCR方法检测Fas,Fas配体,caspase10p20,caspase8,I κB α和p I κB α蛋白及mRNA表达。结果 双苯氟嗪明显降低海马CA1区免疫阳性细胞数量及Fas,Fas配体,caspase10p20蛋白表达 (P<0 01),且呈剂量依赖性(20和 40mg·kg-1组,r=0 92,P<0 01);显著降低Fas及Fas配体mRNA表达(P<0 01);caspase8和I κB α蛋白表达在给药前后无显著变化 (P>0 05 );未能检测出p I κB α蛋白表达。结论 双苯氟嗪通过抑制CD95分子启动的死亡信号转导通路发挥其抗脑缺血再灌注损伤作用;这一作用与转录因子NF κB无关。
Objective To study the mechanism of dipfluzine against global cerebral ischemia-reperfusion injury in rats. Methods Rats were subjected to global ischemia 15 min and then to reperfusion 3 d. Dipfluzine (20, 40 and 80 mg · kg -1, ig) was given after reperfusion. Immunohistochemistry was used to observe the molecular localization of Fas and Fas ligand. The expressions of Fas, Fas ligand, caspase 10p20, caspase8, IκBα and p IκBα protein and mRNA were detected by Western blotting and RT-PCR. Results Dipfluzine significantly decreased the number of immunoreactive cells and the expression of Fas, Fas ligand and caspase 10p20 in CA1 area of hippocampus (P <0.01) in a dose-dependent manner (20 and 40 mg · kg-1, r = 0 92 , P <0.01). The mRNA expression of Fas and Fas ligand was significantly decreased (P <0.01). The expressions of caspase8 and IκBα were not significantly changed before and after administration (P> 0.05) κB α protein expression. Conclusion Dipfluzine exerts its anti-cerebral ischemia-reperfusion injury by inhibiting the death signal transduction pathway initiated by CD95 molecule, which has nothing to do with the transcription factor NF κB.