甲基汞对大鼠胚胎细胞毒性和相关基因表达的影响  

Effects of Methylmercury on Embryonic Cell Behavior and Expression of Related Gene

作　　者：李勇[1,2,3] 李松[1,2,3] 赵如冰[1,2,3] 陈星 潘漪清[1,2,3] 孙棉龄 李竹[1,2,3] 

机构地区：[1]北京医科大学中国妇婴保健中心 [2]上海计划生育研究所 [3]华西医科大学公共卫生学院

出　　处：《中华预防医学杂志》1999年第2期81-84,共4页Chinese Journal of Preventive Medicine

基　　金：国家自然科学基金;中国博士后科学基金

摘　　要：目的从细胞和基因水平揭示甲基汞的发育毒性作用机理。方法应用体外／体内大鼠模型、原位杂交等方法观察甲基汞（体外染毒剂量依次为０、０．０５、０．１０、０．２０、０．４０、０．８０和１．６０ｍｇ／Ｌ；体内染毒剂量依次为０、０．２、０．４、０．８、１．６和３．２ｍｇ／ｋｇ）对９．５天龄大鼠胚胎细胞行为和基因表达的影响。结果甲基汞能通过卵黄囊胎盘，但高浓度可抑制胎盘发育和血管分化；甲基汞对胚胎的发育毒性与其浓度间存在剂量反应关系，胚胎畸形的主要表现是神经管未闭和体位异常。甲基汞能激发胚胎细胞过度凋亡，明显抑制细胞ＤＮＡ和ＲＮＡ的合成，损害胚胎细胞超微结构。甲基汞能诱发热休克蛋白７０基因大量表达，抑制纤维连接蛋白基因和ｐ１６基因的表达；热休克蛋白７０基因、Ｃａ２＋、细胞凋亡与畸形的发生之间具有相关性。结论胚胎细胞行为和相关基因表达异常在甲基汞的发育毒性作用机理中起重要作用。Objective To explore the mechanism of embryonic developmental toxicity of methyl mercury at cellular and gene levels. Methods Effects of methylmercury on embryonic cell behavior and gene expression in rats were observed with in vitro (0,0.05,0.10,0.20,0.40,0.80 and 1.60 mg/L of methylmercury)and in vivo (0,0 2,0.4,0.8,1.6 and 3.2 mg/L of methylmercury) rat models,in situ hybridization and TdT induced dUTP nick end labeling techniques. Results Methylmercury could pass through yolk sac placenta quickly,and inhibit placenta development and blood vessel differentiation there at higher concentration.There was a dose response relationship between concentration of methylmercury and its embryonic developmental toxicity.Its developmental toxicity mainly characterized as patent neural tube and anomalous flexion.Methylmercury could induce excessive apoptosis of embryonic cells,inhibit apparently the synthesis of cellular DNA and RNA and damage its cellular ultrastructure.It also could induce significantly the expression of heat shock protein 70 mRNA and inhibit the expression of fiberonectin and p16 mRNA.There was relationship between heat shock protein 70 mRNA,Ca 2+ ,apoptosis and teratogenesis.Conclusion Disturbance of embryonic cell behavior and related gene expression played important roles in developmental toxicity caused by methylmercury.

关 键 词：毒性 甲基汞化合物 胎儿发育 胚胎细胞毒性 

分 类 号：R995[医药卫生—毒理学]