基于PPARs-NF-κB信号传导通路探索瘀胆肝损伤机制及参芪扶正保护作用的研究

项目名称： 基于PPARs-NF-κB信号传导通路探索瘀胆肝损伤机制及参芪扶正保护作用的研究

项目编号： No.81473504

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 巩鹏

作者单位： 大连医科大学

项目金额： 73万元

中文摘要： 瘀胆肝损伤机制目前尚未完全阐明，临床缺乏有效的治疗手段。本课题组研究证实PPARs-NF-κB信号通路在瘀胆肝损伤中起着关键的调节作用，黄芪对瘀胆肝具有保护作用。但这一信号传导通路在瘀胆肝损伤中具体调控机制尚不清楚，骨髓间充质干细胞（BMSCs）及参芪扶正注射液（SFI）虽能够作用于NF-κB，但能否通过调控PPARs-NF-κB信号通路发挥治疗作用？本课题拟在瘀胆肝大鼠模型及体外实验中深入研究PPARs-NF-κB信号通路在瘀胆肝损伤中的作用，明确这一信号通路在瘀胆肝损伤中与氧化、炎症、凋亡、自噬及纤维化间的关系及调控机制，探讨SFI联合BMSCs治疗瘀胆肝损伤的效果及机制，并明确SFI能否通过提高BMSCs定植率、转化率及促进其向肝细胞分化，而增强其治疗效果。课题将为瘀胆肝损伤机制及中药结合BMSCs移植治疗瘀胆肝损伤提供实验及理论依据，也将为瘀胆肝这一临床难题提供新的治疗途径。

中文关键词： 过氧化物酶体增殖物激活受体；核因子-κB；胆汁淤积性肝损伤；参芪扶正注射液；调控机制

英文摘要： The mechanism of cholestatic liver injury remains unclear and lead to the difficulty of treatments. Our studies have demonstrated that PPARs-NF-κB signaling pathway may be the key regulatory factor in cholestatic liver injury, and astragalus mongholicus could ameliorate cholestatic liver injury, improve the inflammatory environment of liver, but the exact mechanism is obscure. Although Bone marrow-derived mesenchymal stem cells (BMSCs) and Shenqi Fuzheng injection (SFI) plays an important effect in the regulation of NF-κB in treatment of cholestatic liver injury, what is the role of PPARs-NF-κB signaling pathway in the treatment? So the purpose of this study is to investigate the role of PPARs-NF-κB signaling pathway in cholestatic liver injury and protective effect of BMSCs combine with SFI in treatment. On the basis of the in vivo and in vitro experiments, we will investigate the regulative mechanism of PPARs and NF-κB in cholestatic liver injury and treatment of BMSCs combine with SFI, assess the efficacy of SFI and BMSCs, explore the reasonable therapeutic principle for cholestatic liver injury, and search for novel regulatory factors. Moreover, we will also study that whether or not SFI could promote proliferation, migration, differentiation, and improve the low implantation rate and limited conversion rate of BMSCs. Our research will offer the experimental and theoretical basis for the mechanism of cholestatic liver injury and therapy of BMSCs combine with SFI, and also create a new therapeutic approach for cholestatic liver disease.

英文关键词： Peroxisome proliferator-activated receptors(PPARs);Nuclear factor-κB(NF-κB);cholestatic liver injury;Shenqi Fuzheng injection(SFI);regulation mechanism