基于调控TGF-β1/wnt/β-catenin与PPARγ通路的金水缓纤方治疗肺纤维化的机制

特发性肺间质纤维化（IPF）严重危害公众健康，缺乏有效治疗手段。肺泡损伤修复中致纤维化与抗纤维化的平衡紊乱是其主要病理生理环节。本研究基于“正虚络痹积损”的病机及确证的金水缓纤方临床疗效，拟开展①以肺纤维化大鼠模型为研究对象，采用免疫组化、激光共聚焦、qPCR等技术，测定肺功能、纤维化相关因子（CTGF、Fn1、α-SMA等）、信号通路（TGF-β1、Wnt1、β-catenin、PPARγ等）指标；②采用β-catenin基因沉默和PPARγ慢病毒激活方法，以TGF-β1诱导的A549和MRC-5细胞为对象，应用免疫荧光、免疫蛋白印记等技术，观察上皮间质标志物（E-cadherin、Fn1、α-SMA等）、信号通路（Smad3、Wnt1、β-catenin等）指标变化。围绕TGF-β1/wnt/β-catenin与PPARγ通路，阐释金水缓纤方治疗肺纤维的机制，为临床应用提供依据。

Idiopathic pulmonary fibrosis (IPF) is a major disease in the world with severely damage in public health, while there are no effective treatments. The balance disturbance of fibrosis and anti-fibrosis in alveolar damage repair is the key point of the pathogenesis. Based on Chinese medicine theory and confirmed clinical curative effect of Jinshui Huanxian Granules, the following researches will be carried out: ①To observe the effects of Jinshui Huanxian Granules in IPF rats model and explore the mechanism by measuring lung function, pulmonary pathology, fibrosis factors (CTGF, Fn1, α-SMA) and the indicators of signaling pathway (TGF-β1, Wnt1, β-catenin, PPARγ); ②To explore the effects of Jinshui Huanxian Granules in A549 and MRC-5 cell line and its mechanism in alveolar damage repair by using the technologies of β-catenin gene silencing and PPARγ slow virus activation and measuring EMT(E-cadherin,Fn1,α-SMA), as well as the relevant genes and proteins expressions of signaling pathway. The aim of this study is to explore the mechanism of Jinshui Huanxian Granules via TGF-β1/Wnt/ β-catenin and PPARγ signaling pathways and provide a basis for clinical application.