人精子染色体受氯氮平影响的实验观察(英文)  

Effect of clozapine on human sperm chromosomes in vitro

作　　者：蒙华庆[1] 

机构地区：[1]重庆医科大学附属第一医院心理卫生中心,重庆市400016

出　　处：《中国临床康复》2006年第46期218-219,共2页Chinese Journal of Clinical Rehabilitation

基　　金：国家自然科学基金资助项目(39270810)~~

摘　　要：背景:氯氮平为精神科常用抗精神病药物,有报道该药物会引起人体细胞染色体畸变,本文进一步分析其对人生殖细胞的诱变性及生殖遗传毒性。目的:应用人精子染色体离体测试系统研究氯氮平对人精子染色体的影响。设计:以离体人精子染色体为观察对象的随机对照观察。单位:重庆医科大学附属第一医院心理卫生中心。材料:人精液标本取自半年内未接触过理化诱变因子的健康成年男性,氯氮平原药粉为上海第九制药厂生产,鼠卵取自6～8周龄的雌金黄地鼠,受精和洗涤精卵用培养基为含0.3%人血白蛋白的BWW液,获能用培养基为含3.5%人血白蛋白的BWW液,受精后培养基用含10%地鼠血清的卵培养基。方法:实验前3d给实验地鼠肌肉注射孕马血清促性腺激素40单位/只,58h后肌注人绒毛膜促性腺激素30单位/只。收集精液于无菌小烧杯内,经洗涤、离心、获能后,制作成5mL精子悬液,均分于5支离心管中,一管加入终浓度为40mg/L的平阳霉素作为阳性对照,一管不加任何试剂作为阴性对照,其余3管加氯氮平,终浓度分别为200、400、800μg/L熏取出地鼠卵后,分别用0.1%的透明质酸酶和胰酶去除卵丘细胞和透明带后,平均移入5个培养皿中的一个空白液滴中,用分步固定气干法制备精子染色体。主要观察指标:染色体结构畸变精子率和断裂数。结果:氯氮平浓度分别为200,400,800μg/L时,染色体结构畸变精子率和断裂均数与空白对照组比较差异均无显著性,且3个剂量组组间差异亦无显著性,而平阳霉素40mg/L组和阴性对照组间差异有极显著性(P<0.01)。结论:氯氮平对人精子染色体无损伤作用,人精子染色体离体测试系统主要检测诱变剂对染色体的致断作用,可能氯氮平对精子染色体不具有这种损伤作用,而有其它遗传毒理机制。BACKGROUND： Clozapine is a common antipsychotic drug for treating psychotic patients. Some reports suggest that it can cause chromosomal aberration of human cells. This study was designed to analyze the effect on mutagenesis of human generative cells and genetics toxicity of generative cells. OBJECTIVE： To research the effect of clozapine on human sperm chromosome with testing system ex vivo. DESIGN： Randomized controlled observation on the basis of human sperm chromosome. SETTING： Center of Psychological health, the First Hospital affiliated to Chongqing Medical University. MATERIALS： Human sperm was selected from healthy adult males who were not received mutagenesis factors within half a year. Clozapine was provided by the Ninth Pharmaceutical Factory of Shanghai. Ovum was selected from female golden shrewmouse aged 6-8 weeks. Ovum was fertilized and washed with BWW culture medium containing 0.3% or 3.5% human serum albumin. After fertilization, ovum was cultured with ovi-culture medium containing 10% serum of shrewmouse. METHODS： At three days before experiment, shrewmouse was muscularly injected with 40 unit/ampoule preganat mares esrum gonadotrophin, and then with 30 unit/ampoule human chorionic gonadotrophin. Semen was maintained in aseptic beaker and made 5 mL sperm suspension after washing, centrifugation and capacitation. The suspension was equally put into 5 centrifuged tubes. 40 mg/L bleomycin A5 was added into one tube to regard as positive control, one tube was regarded as negative control without adding any reagent, and other tubes were added with clozapine at the concentrations of 200, 400 and 800 μg/L, respectively. Ovarium mound cells and pellucid zone in ovum were wiped out with 0.1% alidase and pancreatin, and then, equally transplanted into a blank gutta in five culture medium. Sperm chromosome was established with stepped fixed air technique. MAIN OUTCOME MEASURES： Sperm rate and broken amount of chromosomal structural aberration. RESULTS： When concentration of

关 键 词：氯氮平 人 精子 染色体 

分 类 号：R596[医药卫生—内科学]