基于胰岛素信号转导环节的中药组分“HJJB”复方防治非酒精性脂肪肝作用机理研究

On the basis of certain proportion formula of four kinds of effective components with rhodiola glycosides (H), gynostemma total glycosides (J), curcumin (J) and extracted polysaccharide (B) (hereinafter referred to as "HJJB compound") has ideal pharmacodynamics effect of preventing and treating experimental NAFLD and improving hyperinsulinemia which were found in the early stage of the study. NAFLD model of rats induced by single high-fat diet and 3T3-L1 fat cells insulin resistance model were used respectively to reveal mechanism of action of HJJB compound for preventing and treating nonalcoholic fatty liver disease around the key link of insulin signal transduction pathways and its associated mechanism. And the intervention effect and effect of strength of HJJB compound and each component on different pharmacological approach and target were analyzed to reveal combination advantage of effective components compound of traditional chinese medicine. To provide solid foundation of traditional chinese medicine compound of curing NAFLD which has compound multi-channel combination characteristic, clear mechanism of action and clear material base.

在前期研究发现红景天苷（H）、绞股蓝总苷（J）、姜黄素（J）、白术多糖（B）四种有效组分的特定配比组方（简称“HJJB方”）有非常理想的防治实验性非酒精性脂肪肝（NAFLD）药效学效应及改善高胰岛素血症效应的基础上，拟分别运用高脂饮食诱导的大鼠NAFLD模型和3T3-L1脂肪细胞胰岛素抵抗模型，围绕胰岛素信号转导通路及其关联机制的关键环节，揭示HJJB方防治非酒精性脂肪肝的作用机制。并通过分析HJJB方与各单一组分对不同药理途径和靶点的干预效应和效应强度，揭示中药有效组分复方综合作用优势。为研制有复方多途径综合作用特点，作用机理清晰，物质基础明确的抗NAFLD中药复方提供坚实的基础。

随着人们生活方式的改变和生活水平面的提高，NAFLD的发病率逐年提升，已经成为我国的重要肝病之一。积极防治NAFLD具有重要意义，然而，目前尚缺乏有效的治疗手段。本课题在前期证实由红景天苷（H）、绞股蓝总苷（J）、姜黄素（J）、白术多糖（B）特定配比组成的中药组分复方“HJJB方”具有良好的治疗 NAFLD 的疗效的基础上，进一步围绕NAFLD胰岛素信号转导环节的关键病理机制，进行该组分复方的作用机理研究。研究分别运用高脂饮食诱导的大鼠NAFLD模型和油酸钠诱导的HepG2细胞脂肪变性模型，围绕胰岛素信号转导通路及其关联机制的关键环节，揭示HJJB方防治非酒精性脂肪肝的作用机制。获得的主要研究结果如下：1）HJJB方能明显改善NAFLD大鼠胰岛素抵抗，显著抑制NAFLD肝脏脂质沉积，明显上调NAFLD大鼠的肝组织CPT-1、IRS1、pIRS1、PI3K、pPI3K、PKB、pPKB含量，明显下调NAFLD大鼠的肝组织SREBP-1c、ChREBP、ACCase、SCD1含量，提示HJJB方能调控NAFLD胰岛素信号通路进而改善肝脏脂肪代谢；2）HJJB方能明显抑制油酸钠诱导的HepG2细胞脂质沉积，增强胰岛素敏感性，改善胰岛素抵抗进而抑制细胞脂肪合成的关键环节。本课题围绕胰岛素信号转导和脂肪代谢环节，阐明了HJJB方防治NAFLD的作用机制，为开发出作用机理清晰、物质基础明确、制剂可控、疗效明显确切的中药有效组分复方奠定了坚实的基础。