中文摘要
气虚血瘀是高血压肾损害的主要病机之一,补气活血中药黄芪-丹参可明显延缓高血压肾损害的进程,前期研究证实其药理机制涉及多个信号转导通路,microRNA在其中发挥重要的调节作用。本研究拟以自发性高血压大鼠(SHR)和大鼠肾动脉内皮细胞为模型,通过microRNA芯片筛选毛蕊异黄酮-丹参酮ⅡA(黄芪、丹参有效单体)药对的靶microRNA;通过脂质体转染肾动脉内皮细胞、重组慢病毒转染SHR,过表达及敲减miR-21(或miR-29b),体内、体外分别观察毛蕊异黄酮-丹参酮ⅡA药对通过调节miR-21和/或miR-29发挥调节RhoA/ROCK、FAK/PI3K/AKT、SMAD3/TGF-β信号通路的功效,探索验证假说“miR-21(或miR-29b)是毛蕊异黄酮-丹参酮ⅡA药对的直接作用靶点”,对阐明补气活血类中药黄芪-丹参的作用机制,揭示中药的“多靶点效应”具有重要的研究价值和探索意义。
英文摘要
The deficiency of Qi and blood stasis is one of the main pathogenesis of hypertensive nephropathy. The double-drugs compatibility of Salvia miltiorrhiza and Astragalus membranaceus, usually gain desirable efficacy in the treatment of hypertensive nephropathy. The preliminary studies have confirmed its pharmacological mechanism involving multiple signal transduction pathways, in which microRNAs play an important regulatory role. This study is planned to take spontaneously hypertensive rats (SHR) and renal artery endothelial cells as models, screening the target microRNAs of Calycosin - TanshinoneⅡA (C-T, effective monomers of Salvia miltiorrhiza and Astragalus membranaceus) by microRNA chip; the renal artery endothelial cells are transfected by liposome and SHRs are transfected by recombinant lentiviral to overexpress or knockdown of miR-21 (or miR-29b), both in vivo and in vitro, to observe the efficacy of C-T on RhoA/ROCK, FAK/PI3K/AKT, SMAD3/TGF-β signaling pathways by regulating miR-21 and / or miR-29 and to confirm the hypothesis that "miR-21 (or miR-29b) is the target of C-T. This study demonstrates important research value and exploration significance on clarifying the pharmacodynamic mechanism of classic Chinese herbal formula of Buqihuoxue of Salvia miltiorrhiza - Astragalus membranaceus and interpreting the "multi-target effects" of traditional Chinese medicine.
