中文摘要
3-氯-1,2-丙二醇(3-MCPD)是一种广受关注的食品污染物,具有多种毒性,靶标主要是肾脏和雄性生殖系统。前期我们证实,3-MCPD引起人胚肾细胞存活率降低、线粒体呼吸酶表达紊乱、HSPB8表达升高、细胞发生凋亡、且这种凋亡属于caspase依赖型的细胞凋亡;外源芹菜素能够极大的缓解由3-MCPD引起的细胞损伤。本课题拟从体外、体内水平研究芹菜素缓解3-MCPD引起的肾损伤的能力并探讨其机制,重点关注对线粒体呼吸酶、caspase 级联信号系统的影响。另外,利用过表达和RNAi稳定转染细胞系,在细胞水平探讨HSPB8在这种保护效应中的作用。同时,采用iTRAQ技术筛选芹菜素的蛋白靶标,探索相应的作用机制信号网络。本项目的创新性在于首次探讨芹菜素对3-MCPD引起的肾细胞毒性损伤的保护效应,可为解释3-MCPD的毒性作用机制及预防治疗提供有力的科学基础,进而保障人类健康。
英文摘要
3-Chloropropane-1,2-diol (3-MCPD) , one of the chloropropanol compounds that detected in many foods,has shown to be toxic in animals, including neurotoxic, immunotoxic, mutagenic, genotoxic and carcinogenic. The toxic targets of 3-MCPD included kidney and male reproductive system. Our previous study showed that a natural plant compound-apigenin, could reduce cell damage induced by 3-MCPD in HEK293FT cells greatly. The present study plan to better understand the protective effect of apigenin against 3-MCPD both in vitro and in vivo, and to explore the protective mechanism from the function of mitochondrial especially respiratory complex I, II, III, IV and V, as well as caspase cascade signal pathway. In addition, HSPB8, a 22 kD heat shock mitochondrial protein, was up-regulate by 3-MCPD in vitro. So the role of HSPB8 in the protective effect of apigenin in nephrocyte was focused in this study. Meanwhile, in order to screen the detail protective molecular targets of apigenin, the iTRAQ proteome technology should be adopted. The innovation of this project lies in the fact that the renal injury of 3-MCPD was relieved by apigenin for the first time. This study provides the theoretical foundation of 3-MCPD and preventive treatment, and ensures human health.
