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[甲基汞对胚胎细胞行为及相关基因表达的影响]

[Effects of methylmercury on embryonic cell behavior and expression of related gene].

作者信息

Li Y, Li S, Zhao R, Chen X, Pan Q, Sun M, Li Z

机构信息

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

出版信息

Zhonghua Yu Fang Yi Xue Za Zhi. 1999 Mar;33(2):81-4.

Abstract

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 fibronectin 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.

摘要

目的

从细胞和基因水平探讨甲基汞对胚胎发育毒性的作用机制。

方法

采用体外(甲基汞浓度分别为0、0.05、0.10、0.20、0.40、0.80和1.60mg/L)和体内(甲基汞浓度分别为0、0.2、0.4、0.8、1.6和3.2mg/L)大鼠模型、原位杂交及TdT介导的dUTP缺口末端标记技术,观察甲基汞对大鼠胚胎细胞行为和基因表达的影响。

结果

甲基汞可迅速通过卵黄囊胎盘,高浓度时可抑制胎盘发育及血管分化。甲基汞浓度与其胚胎发育毒性之间存在剂量-反应关系。其发育毒性主要表现为神经管开放和异常弯曲。甲基汞可诱导胚胎细胞过度凋亡,明显抑制细胞DNA和RNA合成并损伤细胞超微结构。还可显著诱导热休克蛋白70mRNA表达,抑制纤连蛋白和p16mRNA表达。热休克蛋白70mRNA、Ca(2+)、凋亡与致畸之间存在关联。

结论

胚胎细胞行为及相关基因表达紊乱在甲基汞所致发育毒性中起重要作用。

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