镉诱导大鼠睾丸支持细胞凋亡和DNA甲基化的作用机制研究

项目名称： 镉诱导大鼠睾丸支持细胞凋亡和DNA甲基化的作用机制研究

项目编号： No.21467015

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 化学工业

项目作者： 文春根

作者单位： 南昌大学

项目金额： 53万元

中文摘要： 镉是重金属污染中典型的致毒元素，可以通过蓄积和放大作用对机体组织产生损伤, 也可以引起细胞凋亡。线粒体是内源性凋亡途径的调控中心,线粒体外膜渗透是其中的关键事件。DNA甲基化可以使基因沉默化，进而使基因失去功能。本项目拟建立大鼠镉中毒的试验模型，分离睾丸支持细胞进行体外培养。电镜下观察镉暴露后睾丸支持细胞内线粒体结构的变化，分析线粒体的功能变化及其对细胞凋亡相关基因表达的影响。通过检测镉暴露导致大鼠睾丸支持细胞DNA甲基化水平的变化，阐明镉暴露与 DNA甲基化的关系。从个体、细胞、亚细胞及分子水平，分别检测睾丸支持细胞中线粒体的多种生物学指标，研究其变化与细胞凋亡之间的相关性，以确定线粒体在镉诱导睾丸支持细胞凋亡中可能的介导作用和DNA甲基化的关系，以探讨镉诱导睾丸支持细胞凋亡的分子机理。本项目的完成，将为重金属污染的生物监测提供资料，并为环境毒理学和动物的生殖毒性研究提供可靠依据。

中文关键词： 镉；鼠；线粒体；细胞凋亡；DNA甲基化

英文摘要： Cadmium is a typical toxic element in heavy metal pollution, and can result in tissue damage of organism through the effect of accumulation and amplification, and can also cause tissue cell apoptosis of the organism. The mitochondrion is control center of intrinsic apoptotic pathway, The mitochondrial outer membrane permeability is one of the key events. DNA methylation can cause gene silencing, and then make the gene loss of function. In this project, rat will be as an experimental model of cadmium-poisoned animal and sertoli cells from testis will be separated and cultured in vitro. Changes of the mitochondrion's structure within cadmium-poisoned sertoli cells will be observed by electron microscope. Effects of the mitochondrion's function, expression of apoptosis-related genes will be analyzed by biochemical methods. Changes level of DNA methylation will be detected By rat testis sertoli cells exposure in Cd, and the relationship between Cd exposure and DNA methylation will be clarified. Furthermore, various biological indexes of the cadmium-poisoned mitochondrion from testis will be detected at individual, cell, subcellular and molecular levels, respectively. On the other hand, the relationship between the mitochondrion's changes and apoptosis will be studied to determine the potential mediated role of the mitochondrion during apoptosis induced by Cadmium and DNA methylation level, and investigate its molecular mechanism. The project completed will provide material for the biological monitoring of heavy metal pollution, and will also afford reliable basis for studies on environmental toxicology and animal reproductive toxicity.

英文关键词： cadmium;Rats;Mitochondrion;Apoptosis;DNA methylation