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目的:探讨新型钙增敏剂椒苯酮胺(piperphentonamine,PPTA)对全脑缺血/再灌注损伤大鼠的保护作用。方法:采用四血管阻断法建模。造模成功后,SD大鼠随机分为正常组、模型组、低、中和高剂量PPTA组(2.5,5,10 mg.kg-1)。Morris水迷宫测定大鼠学习记忆能力;Nissl染色观察海马神经元丢失情况;LDH试剂盒检测LDH活力;real-time PCR检测海马bax/bcl-2,caspase-3和iNOS mRNA的表达。结果:与模型组比较,5和10 mg.kg-1PPTA组大鼠逃避潜伏期显著缩短;细胞损伤减轻和LDH的释放减少;bax/bcl-2,caspase-3和iNOS基因表达下调。结论:PPTA能显著减轻脑缺血损伤大鼠海马神经元的凋亡和细胞损伤,并能有效改善其学习记忆能力。
Objective: To investigate the protective effect of piperphentonamine (PPTA), a new calcium sensitizer, on global cerebral ischemia / reperfusion injury in rats. Methods: Four-vessel occlusion method was used for modeling. After successful modeling, SD rats were randomly divided into normal group, model group, low, medium and high dose PPTA group (2.5, 5, 10 mg.kg-1). The learning and memory abilities of rats were measured by Morris water maze; the neuron loss in hippocampus was observed by Nissl staining; the activity of LDH was detected by LDH kit; the expressions of bax / bcl-2, caspase-3 and iNOS mRNA in hippocampus were detected by real-time PCR. Results: Compared with the model group, the escape latency of rats in 5 and 10 mg · kg-1 PPTA groups was significantly shortened; the cell injury was reduced and the release of LDH was decreased; and the expressions of bax / bcl-2, caspase-3 and iNOS genes were down-regulated. CONCLUSION: PPTA can significantly reduce the apoptosis and cell injury of hippocampal neurons in rats with cerebral ischemic injury and can effectively improve their learning and memory ability.