壮药金花茶多糖（CNP)对Fas/Fasl介导的免疫性肝损伤的作用及机制研究

Hepatocyte apoptosis plays an important role in immune-mediated liver injury (IMLI) happening. Camellia Nitidissima Polysaccharides (CNP) which's separated from the Guangxi Zhuang Medicine Camellia Nitidissima. leaves have a good protective effect for IMLI. Unfortunately, its mechanism remains largely unknown. Now, reducing the cytokines level of TNF-α, IL-6, et al.and inhibiting the activation of Fas/FasL and its down-stream signal transduction pathway has become an important way of improving IMLI. We discovered that CNP not only can decrease the content of ALT, AST, AKP in the liver tissues, but also can down-regulate the expression level of TNF-α, IL-6 and Fas/FasL. Therefore, we conjecture that CNP's protective effect on IMLI may be associated with its inhibition on Fas/FasL and its down-stream signal transduction pathway. So, in this research, to expound CNP explicit cellular mechanism on TNF-α, IL-6 and Fas/FasL, we will investigate its protective effect and the regulatory mechanism of Fas/FasL and its down-stream signal transduction pathway for IMLI in vivo and vitro used by histopathological examination, PCR, ELISA, and so on. That will provide a good experimental basis for further clinical research for CNP.

肝细胞凋亡是引起免疫性肝损伤（IMLI）疾病的重要因素。目前，通过降低TNF-α、IL-6等水平，抑制Fas/FasL及其下游信号传导通路活性已成为改善IMLI的重要途径。本课题组研究发现，广西特色壮药金花茶多糖（CNP）不仅能降低肝脏组织ALT、AST、AKP含量，而且还能下调血浆中TNF-α、IL-6等因子和Fas/FasL表达水平，推测其机制可能是通过抑制Fas/FasL及其下游信号传导通路活性来改善IMLI，但其作用机制尚未完全明确。因此，本项目从体外，以D-氨基半乳糖苷（D-GalN）诱导HL-7702、LX-2为肝细胞凋亡模型；体内采用卡介苗（BCG）+脂多糖（LPS）诱导的IMLI小鼠为模型，以病理学分析、ELISA、PCR等技术和方法，系统地研究CNP对IMLI的保护作用，并阐明Fas/FasL凋亡系统及其下游信号传导通路对IMLI的调控机制。

本课题研究对肝细胞凋亡是引起免疫性肝损伤（IMLI）疾病的重要因素。金花茶多糖（Camellia Nitidissima Polysaccharides ，CNP)对免疫性肝损伤 （immune-mediated liver injury，IMLI）有修复作用，并且其作用原理是抑制Fas/Fasl及其下游信号传导通路活性。目前，通过降低TNF-α、IL-6等水平，抑制Fas/FasL及其下游信号传导通路活性已成为改善IMLI的重要途径。本课题组研究发现，广西特色壮药金花茶多糖（CNP）不仅能降低肝脏组织ALT、AST、AKP含量，而且还能下调血浆中TNF-α、IL-6等因子和Fas/FasL表达水平，推测其机制可能是通过抑制Fas/FasL及其下游信号传导通路活性来改善IMLI。因此，本项目从体外，以D-氨基半乳糖苷（D-GalN）诱导HL-7702、LX-2为肝细胞凋亡模型；体内采用卡介苗（BCG）+脂多糖（LPS）诱导的IMLI小鼠为模型，以病理学分析、ELISA、PCR等技术和方法，系统地研究CNP对IMLI的保护作用，并阐明Fas/FasL凋亡系统及其下游信号传导通路对IMLI的调控机制。