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机构地区:[1]南方医科大学药学院药理学系,广州510515
出 处:《中国新药杂志》2012年第4期366-370,共5页Chinese Journal of New Drugs
基 金:国家"重大新药创制"科技重大专项(2011ZX091011-003)
摘 要: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 effect of piperphentonamine(PPTA) on global cerebral ischemia/reperfusion(I/R) injury in rats.Methods: Global I/R injury was induced by four-vessel occlusion in rats.Then the rats were randomly divided into control,I/R,and PPTA(2.5,5 and 10mg·kg-1) groups.Morris water maze was used to evaluate the learning and memory abilities.The histological changes in the hippocampus were observed after Nissl staining.LDH activity and the expression of bax/bcl-2,caspase-3 and iNOS mRNA were measured by colorimetric assay kit and real-time PCR.Results: PPTA(5 and 10mg·kg-1) significantly shortened escape latency in the Morris water maze test,and protected neurons from injury.The LDH activity and the expression of bax/bcl-2,caspase-3 and iNOS were reduced compared with I/R group.Conclusion: PPTA can reduce neuronal damage in the hippocampus,and enhance the ability of learning and memory after global I/R injury in rats.
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