茵陈蒿汤调控转运器MRP2/ISBT抗胆汁淤积的机制研究

胆酸盐转运器在胆汁淤积的发生、发展过程中起核心作用，有效干预其信号转导是目前治疗胆汁淤积的重要策略。课题组前期研究结果提示，影响MRP2蛋白表达可能是茵陈蒿汤治疗胆汁淤积的关键节点，但其确切的调控机制尚不清楚。本项目紧密围绕肝、肾组织中MRP2,ISBT相关调控机制研究进展，提出中医“祛湿利小便”黄疸治疗大法主要机制可能是通过影响细胞因子(TNF-α,IL-1β)→核受体(FXR,SHP-1,LRH-1)→转运器(MRP2,ISBT)这一信号通路，从而起到促进胆酸盐肝、肾排泄的科学假说。选用肝外(BDL)和肝内(ANIT)两种胆汁淤积大鼠模型，通过蛋白印迹、RT-PCR、免疫荧光激光共聚焦、EMSA对调控MRP2,ISBT表达的相关因子进行观测，明确茵陈蒿汤有效干预胆汁淤积的关键调节点及调节机制，证实假说。

Bile salt transporters play the core role in the generation and development of cholestasis; and the effective intervention in their signal transduction is an important strategy for controlling cholestasis. Our previous research indicate that MRP2 protein expression which effect pump function is the key link in the Yinchenhao decoction treatment for cholestasis, but its accurate mechanism is still uncertain. This study closely centered on the development of MRP2, ISBT, propose scientific hypothesis that the main mechanism of removing the dampness and diuretic therapy for jaundice is possibly effect the signal channel of cell factors(TNF-α,IL-1β)→Nuclear hormone receptors(FXR,SHP-1,LRH-1)→transporters (MRP2, ISBT), therefore promoting the liver and renal excretion in bile salt. We combine the BDL and ANIT model rats, use western blot, RT-PCR, confocal immunofluorescence, EMSA confirm whether Yinchenhao decoction regulating transporter expression can effect this signal channel, and explore its mechanism, make sure the key point and regulating mechanism for Yinchenhao decoction effectively intervening cholestasis, confirmed the hypothesis.