中文摘要
microRNA(miR)的转录和转录后调节在肥胖性高血压发生发展中具有重要的作用,其中miR-155是肥胖性高血压选择性瘦素抵抗的重要调节分子之一。临床应用和前期研究显示半夏白术天麻汤具有明确的降压减重药效,但药理机制不明。本研究拟以大鼠主动脉内皮细胞和高脂饲料诱导的肥胖性高血压大鼠为模型,通过miR芯片检测,观察半夏白术天麻汤对ox-LDL-AngII联合诱导的内皮细胞miR表达谱的调节和影响,筛选有效靶miR;通过脂质体转染主动脉内皮细胞、重组慢病毒转染肥胖性高血压大鼠,过表达及敲减miR-155,体内、体外分别观察半夏白术天麻汤通过调节miR-155发挥调节MAPK/ERK、JAK2/STAT3、NF-κB信号通路的功效,探索验证假说“miR-155是半夏白术天麻汤的直接作用靶点”,对阐明半夏白术天麻汤的药理机制,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
MicroRNA (miR) transcription and post-transcriptional regulation play important roles in the pathological process of obesity-related hypertension, in which miR-155 is one of the most important regulatory molecules in selective leptin resistance in obesity-related hypertension. Clinical application and preliminary experimental studies have shown that Banxia Baizhu Tianma decoction (BBT) demonstrates beneficial weight loss and antihypertensive efficacy with vague pharmacological mechanism. This study is planed to take rat aortic endothelial cells and high-fat diet-induced obesity-related hypertensive rats as models, observing the effect of BBT on the microRNA expression profile of ox-LDL -AngII induced aortic endothelial cells and screening the target microRNAs of BBT by microRNA chip; the rat aortic endothelial cells are transfected by liposome and high-fat diet-induced obesity-related hypertensive rats are transfected by recombinant lentiviral to overexpress or knockdown miR-155, both in vivo and in vitro, to observe the efficacy of BBT on MAPK/ERK, JAK2/STAT3 and NF-κB signaling pathways by regulating miR-155 and confirm the hypothesis that "miR-155 is the target of BBT". This study demonstrates important research value and exploration significance on clarifying the pharmacodynamic mechanism of classic Chinese herbal formula of BBT and interpreting the "multi-target effects" of traditional Chinese medicine.
