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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 commonly used antipsychotic drug in psychiatry. It has been reported that the drug causes chromosomal aberrations in human cells. In this paper, the mutagenicity and reproductive genotoxicity on human germ cells were further analyzed. OBJECTIVE: To study the effect of clozapine on the chromosomes of human sperm by using in vitro human sperm chromosome test system. Design: A Randomized Controlled Observation of In Vitro Human Sperm Chromosomes. Unit: First Affiliated Hospital of Chongqing Medical University Mental Health Center. MATERIALS: Human semen samples were obtained from healthy adult men who had not been exposed to physical and chemical mutagens for six months. Clozapine powder was produced by Shanghai No.9 Pharmaceutical Factory. The mouse eggs were obtained from 6-8 week-old female golden hamsters, fertilized and The washing egg culture medium was BWW solution containing 0.3% human serum albumin, the useable culture medium was BWW solution containing 3.5% human serum albumin, and after fertilization, the medium was diluted with egg medium containing 10% hamster serum . Methods: Three days before the experiment, experimental rats were intramuscularly injected with 40 units of pregnant mare serum gonadotropin and only 30 hours after administration of human chorionic gonadotrophin. Collected semen in a sterile small beaker, washed, centrifuged, after being made into 5mL sperm suspension, were divided into 5 centrifuge tubes, one tube was added to a final concentration of 40mg / L of pingyangmycin as a positive control , A tube without any reagent as a negative control, the remaining three tubes of clozapine, final concentrations were 200,400,800 μg / L smoked the hamster ovary, were removed with 0.1% hyaluronidase and trypsin After the cumulus cells and zona pellucida, they were evenly transferred into a blank droplet in five petri dishes and the sperm chromosomes were prepared by air-drying in a stepwise manner. MAIN OUTCOME MEASURES: Chromosomal aberrations Sperm ratio and number of breaks. Results: When the concentrations of clozapine were 200, 400 and 800 μg / L respectively, there were no significant differences in the chromosome aberration rate and the number of fracture between the three groups, There was a significant difference between the 40 mg / L group and the negative control group (P <0.01). CONCLUSION: Clozapine has no effect on human sperm chromosomes. In vitro test system of human sperm chromosomes mainly detects the mutagenic effects of mutagens on chromosomes. It is possible that clozapine does not have such damage on sperm chromosomes, while other inheritance Toxicological mechanism.