水体铜和锌暴露差异性影响矛尾复虾虎鱼脂类代谢机理的比较研究

Fatty liver, a serious syndrome of pathomorphism in liver, widely happens in aquaculture, and greatly threatens fish health and quality. Generally speaking, fatty liver in fish is considered to be related with nutrient-imbalanced formulated diets. However, sponsored by National Natural Science Foundation of China (completed), we have found that waterborne copper (Cu) and zinc (Zn) exposure can differentially influence activities of the key enzymes involved in lipid metabolism of liver in Synechogobius hasta, which in turn increases or reduces the occurrence rate of fatty liver for this fish species. Still, the related mechanism remains unknown. By using the theoretical knowledge and scientific research methods related to toxicology, nutrition, immune histochemistry, Western blot, real-time quantitative PCR and hepatocyte primary culture in vitro, the present project will further investigate the differential effects of waterborne Cu and Zn exposure on lipid metabolism, on several key factors (hormones and transcriptional factors) and signaling pathways involved in the regulation of lipid metabolism in S. hasta. Also, we will further explore the regulatory roles of these key factors in lipid metabolism during waterborne Cu and Zn exposure, and demonstrate the related signaling pathways by which Cu and Zn exposure differentially influences lipid metabolism in S. hasta. The objective of the present project is to elucidate the mechanism of differential lipid metabolism in liver of S. hasta induced by waterborne Cu and Zn exposure, based on lipid metabolism and its regulatory network. Meantime, the present project will provide new insights for lipid deposition, and for the occurrence and control of fatty liver in fish, and also search for new, sensitive and reliable biomarkers for waterborne metal pollution, which will help provide new references for risk assessment and healthy and safe evaluation for waterborne metal elements.

脂肪肝是养殖鱼类普遍发生且危害极大的一种肝病变，通常被认为与营养不平衡的饲料有关。然而，在国家自然科学基金（已结题）的资助下，我们发现水体铜和锌能差异性影响矛尾复虾虎鱼脂类代谢关键酶的活性，进而能增加或降低该鱼脂肪肝的发生率，深入的机理不清楚。本课题拟运用毒理学、营养学、免疫组化、Western blot和实时定量PCR等方法，活体原位和离体实验相结合，研究水体铜和锌对矛尾复虾虎鱼脂类代谢及其关键调控因子和信号通路的影响；探讨关键因子在铜和锌差异性影响该鱼脂类代谢中的调控作用，明确铜和锌差异性影响该鱼脂类代谢的信号通路，从脂类代谢及其调控网络揭示铜和锌差异性影响该鱼脂类代谢的机理及其异同，以及与该鱼脂肪沉积和脂肪肝发生的关系。一方面为鱼类体脂沉积及脂肪肝的发生和控制提供新的研究思路，另一方面寻找新的灵敏可靠的生物标志物指示水体金属元素污染，为其风险管理及生态与健康安全评价提供新的科学依据。

脂肪肝是养殖鱼类普遍发生且危害极大的一种肝病变，通常被认为与营养不平衡的饲料有关。然而，在国家自然科学基金（已结题）的资助下，我们发现水体铜和锌能差异性影响矛尾复虾虎鱼脂类代谢关键酶的活性，进而能增加或降低该鱼脂肪肝的发生率，深入的机理不清楚。本项目采用毒理学、营养学、组织化学、分子生物学和“组学”等方法，活体实验和离体肝细胞培养相结合，克隆得到了矛尾复虾虎鱼与金属元素吸收转运、脂肪沉积、代谢及其调控（如内质网应激及其通路）有关的关键基因（超过20个基因）的cDNA序列，解析了它们的分子特征，探讨了它们的组织表达模式；研究了铜和锌对矛尾复虾虎鱼脂肪沉积和代谢的影响；探讨了胰岛素、PPARα、PPARγ、SREBP-1和AMPK、内质网应激及其通路在金属元素（包括铜和锌）影响脂肪沉积和代谢过程中的作用机制；研究了金属元素复合效应（如铜和镉、铜和铁等）对矛尾复虾虎鱼脂肪沉积和脂类代谢的影响及其相关机制。一方面为鱼类体脂沉积及脂肪肝的发生和控制提供新的研究思路，另一方面寻找新的灵敏可靠的生物标志物指示水体金属元素污染，为其风险管理及生态与健康安全评价提供新的科学依据。