保肺化纤方经lncRNA FENDRR/miR-214/TGF-β1轴抑制肺成纤维细胞激活减轻PM2.5导致的肺纤维化加重机制

特发性肺纤维化（IPF）致残率高、死亡率高、预后不良，PM2.5暴露可显著加剧其进程。IPF发病复杂，且缺乏有效防治手段。TGF-β1/Smad3是该病形成发展的关键通路，可抑制lncRNA FENDRR表达，引起促纤维化miR-214过表达和肺成纤维细胞过度激活，导致病情加剧。保肺化纤方可显著改善IPF临床症状，其机制下调TGF-β1/Smad3通路有关，但对lncRNA和miRNA调控尚不明确。故提出假说：保肺化纤方可经FENDRR/miR-214/TGF-β1轴抑制肺成纤维细胞激活，减轻PM2.5导致的IPF加重。拟以PM2.5暴露的IPF大鼠和肺成纤维细胞MRC-5为对象，以inhibitor/mimics转染、qPCR和western blot等技术，观察该信号轴在PM2.5诱导IPF加重中的作用及保肺化纤方作用机制，为寻找有效治疗手段和中医药作用新靶点提供科学依据和研究基础。

Idiopathic pulmonary fibrosis (IPF) is a disease with high disability rate, high mortality and poor prognosis. The exposures of particulate matter with aerodynamic diameters less than 2.5 microns (PM2.5) can significantly aggravate the progression of the disease. The pathogenesis of IPF is very complex, which resulting in the lack of effective treatments. TGF-β1/Smad3 signaling is a key pathway involved in the mechanism of the disease. Data indicated that it can inhibit the expression of lncRNA FENDRR, causing the excessive activation of pulmonary fibroblasts and the overexpression of profibrotic miR-214, and deteriorate the disease. Previous studies indicated that Baofei Huaxian Formula can significantly improve the clinical syndromes in IPF patients, and the downregulation of TGF-β1/Smad3 signaling might be involved in the mechanisms, however, the relevant lncRNA and miRNA regulation of the pathway remains unclear. So, we hypothesized that Baofei Huaxian Formula can alleviate pulmonary fibrotic aggravation caused by PM2.5 exposures by inhibiting fibroblast activation via lncRNA FENDRR/miR-214/TGF-β1 axis, and observe the regulative mechanisms of Baofei Huaxian Formula by using inhibitors/mimics transfection, quantitative polymerase chain reaction (qPCR) and western blotting technologies, in PM2.5 exposed IPF rats and alveolar epithelial cells (A549) and pulmonary fibroblasts (MRC-5). The results of this study will provide scientific basis and research foundation for seeking effective treatment and new effective targets of Chinese medicine.