左旋黄皮酰胺对冈田酸和β淀粉样肽_(25-35)神经毒性的保护作用  

Protective effect of(-)clausenamide against neurotoxicity induced by okadaic acid and β-amyloid peptide_(25-35)

作　　者：张静[1] 程勇[1] 张均田[1] 

机构地区：[1]中国医学科学院中国协和医科大学药物研究所,北京100050

出　　处：《药学学报》2007年第9期935-942,共8页Acta Pharmaceutica Sinica

摘　　要：探讨左旋黄皮酰胺对冈田酸(okadaic acid,OA)诱导的人神经瘤细胞(SH-SY5Y)和去卵巢(ovariectomy,OVX)及单侧侧脑室注射Aβ25-35所致神经元损伤的保护作用。通过MTT试验、LDH释放测定试验、Hoechst 33258荧光染色试验以及SH-SY5Y细胞检测,考察左旋黄皮酰胺拮抗冈田酸诱导的细胞毒作用。通过避暗试验、电镜检测、Nissl体染色及HE染色,考察左旋黄皮酰胺对去卵巢及侧脑室注射Aβ25-35大鼠神经元的保护作用。左旋黄皮酰胺可明显拮抗冈田酸诱导的细胞毒作用,提高去卵巢及侧脑室注射Aβ25-35大鼠的学习记忆能力,保护海马及皮层神经元。左旋黄皮酰胺可拮抗冈田酸及Aβ25-35诱导的神经毒性,具有神经保护作用。This study is to investigate the protective effect of （-） clausenamide against the neurotoxicity of okadaic acid in SH-SY5Y cell line, and injection β-amyloid peptide（25-35） （Aβ（25-35）） to the cerebral ventricle in ovariectomy （OVX） rats. MTT assay, LDH assay, and Hoechst 33258 staining were used to detect the effect of （ - ）clausenamide on the toxicity of okadaic acid in SH-SY5Y cell line. The animal model was induced by ovariectomized and injection of Aβ（25-35） in the cerebroventricle of rats. The effect of （ - ）clausenamide on learning and memory deficiency was observed by step-through test. Electron microscope, Nissl body staining, and HE staining were used to examine the morphological changes in hippocampus and cerebral cortex neurons. Pretreatment of （ - ）clausenamide and LiCl decreased the rate of cell death from MTT, LDH release, and apoptosis from Hoechst 33258 staining in SH-SY5Y cell line. The step-through tests showed （ - ）clausenamide could improve the ability of learning and memory. The Nissl body staining and HE staining experiments also showed the neuroprotective effects of （-） clausenamide on the neurons of hippocampus and cerebral cortex. （ - ）Clausenamide has the protective effects against the neurotoxicity induced by okadaic acid and Aβ（25-35）.

关 键 词：左旋黄皮酰胺 阿尔茨海默病 冈田酸 β淀粉样肽(25-35) 神经保护作用 

分 类 号：R282.71[医药卫生—中药学] R964[医药卫生—中医学]