基于自噬调节上皮间质转化探讨肺痿冲剂治疗特发性肺纤维化的机制研究

IPF is a disease which prognosis is poor, special effects drug therapy is lacking,TCM treatment has great potential.Preliminary clinical studies have shown that Feiwei granules of Yi qi huo xue Chinese Herbal Medicine is effective in treating IPF.In vitro studies have shown that Feiwei granules can regulate epithelial-mesenchymal transformation (EMT) through MAPK signaling pathway, thereby slowing the progression of pulmonary fibrosis.Autophagy plays an important role in repair of tissue damage, and studies have shown that enhanced autophagy can regulate EMT to reduce pulmonary fibrosis.We hypothesize that Feiwei granules can be involved in regulating the treatment of IPF by affecting autophagy.Our research group intends to clarify the mechanism of IPF by the level of molecular, cell, tissue and animal.To explore the mechanism of autophagy regulating EMT;To determine the mechanism of Feiwei granules interfering with IPF which regulating EMT by autophagy .This study will discuss the mechanism of Feiwei granules for the treatment of IPF from autophagy, and provide scientific basis for the prevention and treatment of IPF, and lay a foundation for the development of new drugs.

特发性肺纤维化（IPF）预后较差，临床缺乏特效药物治疗，中医药对其治疗有较大潜力。前期临床研究表明，益气活血中药肺痿冲剂治疗IPF有效。体外实验研究证明，肺痿冲剂可通过MAPK信号通路调节上皮间质转化（EMT）从而减缓肺纤维化进程。自噬在组织损伤修复中发挥重要作用，有研究表明通过增强自噬可调节EMT减轻肺纤维化。我们猜测肺痿冲剂可以通过影响自噬参与调节EMT治疗IPF。本课题组拟从分子、细胞、组织及动物水平多层次明确肺痿冲剂治疗IPF的机制；探讨自噬调节EMT的机制；确定肺痿冲剂通过对自噬的调控，发挥调节EMT的作用从而有效干预IPF的机制。本研究将从自噬这个热点探讨肺痿冲剂的治疗机制，为IPF的防治提供科学依据，并奠定新药研制的基础。

特发性肺纤维化是一种慢性、难治性肺疾病，其形成机制之一为上皮-间质转化。近年来研究表明肺纤维化的自噬水平降低，激活自噬可以抑制上皮-间质转化，改善肺纤维化。肺痿冲剂是一种经验性的中药复方，已被多中心临床研究证明可有效改善特发性纤维化患者临床症状、生活质量等。使用体外转化生长因子β1诱导的A549细胞上皮-间质转化模型及体内博来霉素诱导的C57BL/6N小鼠肺纤维化模型，探索肺痿冲剂对肺纤维化及上皮间质转化的调节作用及与自噬活性的关系。肺痿冲剂对体内TGF-β1诱导的上皮-间质转化及体外博来霉素诱导的肺纤维化均有一定的抑制作用，这种抑制可能与激活的自噬有关。提示自噬不足是肺纤维化的潜在机制，肺痿冲剂可能促进自噬以减轻肺纤维化的发展。