摘要
为探讨氯化甲基汞（ｍｅｔｈｙｌｍｅｒｃｕｒｙｃｈｌｏｒｉｄｅ，ＭＭＣ）致畸作用的分子机理，本实验应用非放射性原位杂交和免疫组化半定量分析等方法研究了ＭＭＣ对９．５天龄大鼠胚胎５种基因及编码产物的影响。结果显示：染ＭＭＣ各组（０、０．２、０．４、０．８、１．６和３．２ｍｇ／ｋｇ）均未见母鼠有明显的中毒症状和死亡。随着染毒剂量的增加，胚胎形态总得分逐渐降低，畸胎率和发育迟缓率不断增高，最高分别达３４％和７６％；诱生型一氧化氮合成酶（ｉｎｄｕｃｉｂｌｅｎｉｔｒｉｃｏｘｉｄｅｓｙｎｔｈａｓｅ，ｉＮＯＳ）ｍＲＮＡ及其编码蛋白和ＨＳＰ７０ｍＲＮＡ表达明显增强，ＮＴｍＲＮＡ及其编码蛋白表达水平下降，均呈明显剂量—反应关系。此外，ＭＭＣ还抑制ＴＧＦβｍＲＮＡ的表达，但对Ｂｃｌ－２ｍＲＮＡ及其编码蛋白表达的影响不明显。基于胚胎形态、基因和蛋白质表达的结果大体一致，相互佐证。
The present study further revealed the teratogenic mechanism of methylmercury chloride(MMC) during rat neurulation by means of nonradioactive in situ hybridization (ISH),semiquantitative analysis of immunohistochemical staining and in vivo teratogenic test.The main aim was to teat the hypothesis that iNOS,HSP70,NT,TGF β and Bcl 2 genes contribute to MMC induced day 9 5 embryonic damages.Results showed there were no obvious poisoning signs and death of pregnant female rats injected intraperitoncally with 0,0 2,0 4,0 8,1 6 and 3 2 mg/kg MMC.While the doses increased,the total morphological scores decreased gradually,and the rates of embryo deformity and development delay increased step by step to 34% and 76% respectively.The levels of iNOS mRNA and protein and HSP70 mRNA increased,and NT mRNA with its protein became down,all these changes were concentration dependent.In addition,MMC could inhibit the level of TGF β mRNA,but no obvious influence on the levels of Bcl 2 mRNA and Bcl 2 protein.On the basis of parallel findings from embryos,genes and proteins,abnormal expression of genes in transcriptional level might be related to MMC induced teratogenic insult.
出处
《卫生研究》
CAS
CSCD
北大核心
1998年第5期306-308,共3页
Journal of Hygiene Research
基金
国家自然科学基金
关键词
甲基汞
致畸机理
胚胎
基因
蛋白质
分子机理
methylmercury,\ teratogenic mechanism,\ embryo,\ gene,\ protein,\ insitu hybridization
