噻萘普汀预处理对甲基苯丙胺神经毒性的影响(英文)

Tianeptine pretreatment for the neurotoxity of methamphetamine

背景:甲基苯丙胺对中枢神经系统具有毒性,5-羟色胺再摄取增强剂噻萘普汀对甲基苯丙胺所致5-羟色胺能神经元的损害是否具有保护效应尚不清楚。目的:探讨甲基苯丙胺的神经毒性及噻萘普汀的神经保护作用和机制。设计:以动物为研究对象,随机对照的实验研究。单位:一所大学的动物研究室和病理研究室。材料:实验于2003-06/08在四川大学实验动物中心、四川大学华西医院分子病理实验室完成。选择Wistar雄性大鼠25只,腹腔注射甲基苯丙胺建模,甲基苯丙胺由中国药品生物制品检定所提供。噻萘普汀为法国施维雅药厂惠赠(批号OE3086)。脱氧核糖核酸末端转移酶介导的缺口末端标记检测试剂盒购自Boehringermannheim公司。干预:设立对照组和实验组(A,B,C,D),A组腹腔注射甲基苯丙胺;B,C,D组分别在给予甲基苯丙胺前7,4d和同时给予噻萘普汀;对照组注射等体积生理盐水。实验后采用苏木精-伊红染色、银染色,光镜观察神经元形态学变化;脱氧核糖核酸末端转移酶介导的缺口末端标记法检测凋亡细胞。主要观察指标:各组动物脑组织切片苏木精-伊红染色、银染色结果和脱氧核糖核酸末端转移酶介导的缺口末端标记阳性神经元计数。结果:甲基苯丙胺可损害神经元的轴突、树突,银染阳性细胞吸光度为50.74±1.86;并诱导凋亡,每高倍视野凋亡细?

BACKGROUND:Methamphetamine(MA) has neurotoxic effects to central nervous system. However, as the 5 hydroxytryplamine reuptake enhancer,it is uncertain that if there are protective effects of tianeptine to the damages of 5 hydroxytryp taminergic neurons caused by MA. OBJECTIVE:To investigate the neurotoxicity of MA and the neuroprotective effects of tianeptine as well as the acting mechanism. DESIGN:Randomized case control study based on animals. SETTING:Animal research room and pathology research room of a university. MATERIALS:The experiment was completed in the Experimental Animal Centre of Sichuan University and Molecular Pathology Laboratory of West China Hospital during June to August 2003.Totally 25 male Wistar rats were injected MA through abdominal cavity to build model. Methamphetamine was provided by National Institute for the Control of Pharmaceutical and Biological Products(NICPBP) while tianeptine was given by French Servier Company (Batch No. OE3086).The TUNEL testing kit was purchased from Boehringer Mannheim Company. INTERVENTIONS:There were one control group and four experimental groups(A,B,C,D).A group was used intraperitoneal injection of MA while B, C,D,groups were administered tianeptine 7 days,4 days before and the same day of MA administration.Normal saline with same volume was injected into rats of control group.HE stain and silver stain were conducted after experiment to observe the morphologic changes of neurons.And TUNEL method was used to detect apoptotic cells. MAIN OUTCOME MEASURES:The HE stain and silver stain of brain tissue sections and counts of TUNEL positive neurons. RESULTS:MA could damage the axon and dendrite of neurons and the absorbance of silver positive cell was(50.74±1.86).It could also induce cell apoptosis while the apoptotic cell count every high power field was 29.26±4.14.There were less apoptotic cells in the group with 7 days usage of tianeptine with the cell count of(18.90±1.60) per high power field. CONCLUSION:MA can cause neurotoxicity by inducing cell apoptosis. And giving tianeptine in advance can protect neurons.