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[甲基汞对大鼠早期胚胎发育分子致畸机制的研究]

[Studies on molecular teratogenic mechanism of methylmercury in early developing rat embryos].

作者信息

Li Y, Zhang T, Wang L, Li Z

机构信息

National Center for Maternal and Infant Health, Beijing Medical University, Beijing 100083, China.

出版信息

Wei Sheng Yan Jiu. 1998 Sep 30;27(5):306-8.

Abstract

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-beta 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-beta 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.

摘要

本研究通过非放射性原位杂交(ISH)、免疫组化染色的半定量分析及体内致畸试验,进一步揭示了氯化甲基汞(MMC)在大鼠神经胚形成过程中的致畸机制。主要目的是验证如下假说:诱导型一氧化氮合酶(iNOS)、热休克蛋白70(HSP70)、神经营养素(NT)、转化生长因子β(TGF-β)和Bcl-2基因与MMC诱导的9.5日龄胚胎损伤有关。结果显示,腹腔注射0、0.2、0.4、0.8、1.6和3.2mg/kg MMC的孕鼠无明显中毒迹象及死亡。随着剂量增加,胚胎总体形态评分逐渐降低,胚胎畸形率和发育迟缓率逐步上升,分别达34%和76%。iNOS mRNA和蛋白水平以及HSP70 mRNA升高,而NT mRNA及其蛋白水平降低,所有这些变化均呈浓度依赖性。此外,MMC可抑制TGF-β mRNA水平,但对Bcl-2 mRNA和Bcl-2蛋白水平无明显影响。基于胚胎、基因和蛋白质方面的平行研究结果,转录水平上的基因异常表达可能与MMC诱导的致畸损伤有关。

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