中文摘要
申请人研究领域是金属元素毒理与鱼类脂类代谢及脂肪肝发生与控制。目前所取得的成果主要包括:(1)克隆得到了鱼类与脂类代谢有关的一批基因cDNA序列(以及部分基因的基因组序列),发现鱼类所特有的一些基因;(2)在国际上率先开展了水体金属元素与鱼类脂肪沉积及脂类代谢关系的研究;较系统地开展了金属元素对鱼类脂类代谢的影响与金属元素种类、暴露浓度和时间、暴露途径及其鱼种的关系,发现新的生物标志物指示水体金属元素污染;(3)建立了鱼类几种脂类代谢关键酶分离纯化的方法,探讨了这些酶的酶学性质和动力学特征、及对金属元素的响应;(4)建立了几种鱼类肝细胞原代及传代培养技术体系,建立了肝细胞脂肪沉积的金属元素诱导模型。发表SCI源刊论文54篇,被SCI论文引用425次。其中以第一作者和/或通讯作者发表SCI源刊论文45篇(被SCI源刊论文引用285次,单篇最高引用34次)。
英文摘要
My research field is involved in metal element toxicity and lipid metabolism, and fatty liver occurrence and control in fish. At present, my work included: (1) to clone some key genes involved in lipid metabolism in fish, and find some new isoforms and alternative spliced forms of genes; (2) to conduct a series of experiments involved in the effect of metal elements on lipid metabolism and deposition, and in the relationship between metal element kinds, exposure concentration and time, exposure pathway, and the fish species, and find some new biomarkers and genes involved in lipid metabolism to indicate the metal toxicity; (3) to successfully build the method for separating and purifying several key enzymes invovled in lipid metabolism in fish, explore their characterization and kinetics, and investigate the effect of several metal elements on their kinetic properties. (4) to build the method of primary hepatocytes culture of several fish. Up to date, I have published 54 SCI papers, consisting of 45 SCI papers with Zhi Luo as the first author and/or corresponding author. Among these papers with Zhi Luo as the first and/ or correspondnig author, they were cited 285 times by SCI journals with one paper cited 34 times by SCI journals.
结题摘要
矿物元素与脂肪沉积及代谢的关系是近年来新出现的研究领域,吸引了国际上广泛的关注和重视,但是相关机理的研究十分缺乏。我们前期研究发现矿物元素能广泛影响鱼类的脂肪沉积和代谢,进而对其脂肪肝的发生造成影响。本项目拟在我们前期大量研究的基础上,采用毒理学、营养学、分子生物学和细胞培养、siRNA干扰、细胞转染和激光共聚焦显微镜等方法和研究手段,阐明了铜和锌在黄颡鱼 Peltoebagrus fulvidraco 体内的吸收和转运机制;揭示了铜和锌对内质网应激(ERS) 及其通路、细胞自噬和凋亡通路的影响,以及与脂肪沉积和脂类代谢的关系;揭示了 ERS 及其通路在铜和锌差异性影响黄颡鱼脂类代谢中的作用机制,从脂类代谢上游调控通路的角度揭示铜和锌影响鱼类脂类代谢的机理。本项目拓展人们对矿物元素致毒机理及鱼类脂肪肝发生途径的认识,有助于寻找新的灵敏可靠的生物标志物指示水体矿物元素污染,并为鱼类脂肪肝的防治提供新的策略和理论依据。
