新型胆碱酯酶抑制剂对阿尔茨海默病作用的生物化学研究  

Biochemical effect of a novel acetylcholinesterase inhibitor on Alzheimer diseas e

作　　者：赖红[1] 叶和珏[2] 赵海花[1] 高杰[1] 刘素媛[3] 王铁民[1] 金大成[1] 吕永利[1] 

机构地区：[1]中国医科大学脑研究所神经解剖研究室,辽宁省沈阳市110001 [2]中国科学院广州化学研究所,广东省广州市510650 [3]中国医科大学基础医学院生化教研室,辽宁省沈阳市110001

出　　处：《中国临床康复》2005年第1期52-53,共2页Chinese Journal of Clinical Rehabilitation

摘　　要：目的:探讨新型胆碱酯酶抑制剂(活性物质)对阿尔茨海默病(Alzheimerdisease,AD海马结构的生物化学影响,为AD患者的临床治疗提供可)靠的基础研究资料。方法:实验选用40只3～5月龄雄性Wistar大鼠,其中30只大鼠切断穹窿海马伞制作AD动物模型。术后第8天静脉给予新型胆碱酯酶抑制剂进行治疗,然后采用分光光度计对各组海马结构分别进行生化检测。结果:海马结构细胞胞浆的乙酰胆碱酯酶(AchE)活性测定:活性物质组的酶活A/蛋白A的均值为0.223±0.058,每毫克蛋白酶活A为0.881±0.051。单纯损伤组分别为0.402±0.193和1.558±1.299,两组比较差异有显著性意义(P<0.01)。红细胞膜AchE活性测定:单纯损伤组的酶活A/蛋白A的均值为0.62±0.09。给药后的活性物质组为0.55±0.08,石杉碱甲组为0.62±0.14。活性物质组与单纯手术组比较差异有显著性意义(P<0.01)。结论:新型胆碱酯酶抑制剂(活性物质)具有较强的抑制乙酰胆碱酯酶的作用,其抑制作用大于石杉碱甲,并对AD具有一定的治疗作用。AIM:To investigate the biochemical effects of a noval acetylcholinesterase inh ibitor(NAI)(activity substance)on Alzheimer disease(AD) in hippocampal formation and provide basic scientific data for the clinical treatment of AD patients. METHODS: Forty male Wistar rats of 3-5 months old were selected. Among them, 30 AD rats' models were established with cutting off fornix fimbria of hippocamp us. The eighth day after operation, rats were treated with intravenous injection of NAI and the hippocampal formations in each group were tested biochemically w ith spectrophotometer. RESULTS: Assay of AchE activity in cell plasma of hippocampal formations: Acti vity of enzyme/protein in activity substance group was all(0.223±0.058), and en zyme per mg protein was (0.881±0.051). Those in simple injured group were(0.40 2±0.193) and(1.558±1.299) respectively, which was significant difference betwe en two groups(P< 0.01). Assay AchE activity in red cell membrane: Activity of en zyme/protein in simple injured group was all (0.62±0.09), but after medication , it was (0.55±0.08) in activity substance group, and (0.62±0.14) in huperzine A group. There was significant difference between activity substance group and simple injured group (P< 0.01). CONCLUSION:The NAI (activity substance) can inhibit the effect of acetylcholin esterase greatly, and the inhibitive effect is stronger than that of huperzine A , so it has a certain effect in AD treatment.

关 键 词：阿尔茨海默病 胆碱酯酶抑制剂 乙酰胆碱酯酶 海马 红细胞膜 

分 类 号：R749.1[医药卫生—神经病学与精神病学]