环境镍暴露对大鼠代谢损伤的生态毒理学研究

镍暴露通过对水、空气、土壤的污染日渐成为威胁生态环境和人类健康的热点，由于其对机体内分泌代谢状态的干扰效应，已被列入内分泌环境干扰物之一。内分泌腺体特别是甲状腺和胰腺通过严密反馈机制调控着机体三大物质的代谢平衡，是能量代谢的核心调控器官。镍与机体代谢调控及胰腺、甲状腺损伤间的研究属于镍污染对生态破坏与机体损伤的一个交叉点。本课题拟以Wistar 大鼠为受试对象，采用化学发光技术、组织形态学分析等方法，检测镍暴露环境下大鼠糖脂代谢变化、甲状腺功能与胰岛功能状态、组织形态学变化，探讨镍暴露环境对机体能量代谢与相关调控腺体的损伤程度；并同步采用免疫组化、RT-PCR、流式细胞术检测这两种腺体中Caspase-3、Bax/Bcl-2、Fas/FasL在mRNA和蛋白水平的表达及凋亡细胞，进一步探讨环境镍暴露代谢损伤的可能机制，为今后相关防护工作的开展提供科学依据。

Nickel exposure through the water, air and soil pollution has become a serious threat to the ecological environment and human health, because of its interference effect on the body's endocrine metabolic state, it had been considered as one of the Environmental Endocrine Disruptors. Endocrine glands, especially the thyroid and pancreas, are the core organs of energy metabolism regulation, they balance the metabolism of carbohydrate, fat and protein through strict feedback mechanism. The study of metabolic regulation and the lesions of pancreas and thyroid is an intersection of the ecological destruction and the body injury caused by nickel pollution. Our study plans to take Wistar rats as subjects, using chemiluminescence technology, morphological analysis and immunohistochemical methods to detect the glucolipid metabolic changes, thyroid function, islet function state, and histomorphology changes of rats exposed to nickel environment, and discuss the effects of environmental nickel exposure on energy metabolism and the related organs. At the same time, we will detect the apoptotic cells, and the expression of Caspase-3, Bax/Bcl-2 and Fas/FasL on both mRNA level and protein level, using RT-PCR, immunohistochemical method and flow cytometry, to explore the possible mechanism of metabolic damage caused by environmental nickel exposure, and provide scientific evidence for relevant protection work in the future.