中文摘要
特发性肺纤维化是一种原因不明的,慢性进展性、致死性肺疾病。中医药在肺纤维化的治疗中显出不可替代的优势。ROCK信号通路在肺纤维化的发病过程中具有显著的作用,参与肺纤维化形成过程中的多个环节。肌成纤维细胞的分化在此过程中起关键作用,这都需要ROCK信号通路的激活。因此通过干预ROCK通路,降低肌成纤维细胞的分化可能是一种抑制肺纤维化的有效方法。基于“肺系络病”理论及前期基础,本项目提出“肺纤维化患者存在肺络干血”的假说,通过复制博来霉素致肺纤维化大鼠模型,采用免疫组化、ELISA、Western blot和RT-PCR等方法,在肺纤维化形成过程中和肺纤维化形成后,从器官、细胞、分子、基因等多层次多靶点研究大黄蛰虫丸对肺纤维化大鼠Rho/ROCK信号通路的调控,探讨搜剔肺络法对肌成纤维细胞分化的干预机制,及干血与胶原代谢之间的关系。为临床治疗肺纤维化提供理论依据,进一步丰富搜剔肺络法学术内涵。
英文摘要
Idiopathic pulmonary fibrosis is a chronic, progressive and ultimately fatal pulmonary disease of unknown aetiology. Traditional Chinese Medicine displays invaluable advantages in the treatment of pulmonary fibrosis.The ROCK signalling pathway plays a significant role in the pathogenesis of pulmonary fibrosis and is involved in many aspects of disease development. Differentiation into myofibroblasts, a crucial stage in the pathogenic process, also requires activation through the ROCK pathway. Targeting this pathway could be an effective method to control pulmonary fibrosis.Based on the doctrine of "Lung Luo" and building upon earlier research, this project proposes the hypothesis that pulmonary fibrosis patients have "lung luo dry blood." Using a bleomycin-induced pulmonary fibrosis murine model, the modulation of the Rho/ROCK signalling pathway by Dahuang Zhechong pill is to be assessed, from the organ, cellular, molecular and genetic levels. Immunohistochemistry, ELISA, Western blot, RT-PCR and other molecular biology methods will be employed at different time points, during and after the appearance of fibrosis, to elucidate the mechanism of Soutifeiluo intervention to myofibroblast differentiation and the relationship between dry blood and collagen metabolism.The study would provide the theoretical basis for clinical treatment of pulmonary fibrosis and further enhance the application of Soutifeiluo in the treatment of pulmonary diseases.
