Fas抗体诱导大鼠肺纤维化模型的建立及其干预作用

Pulmonary fibrosis model is the pulmonary fibrosis pathogenesis and the prerequisites of drug therapy. Alveolar epithelial cell apoptosis induce pulmonary fibrosis ,the cause of epithelial apoptosis is not clear, the Fas/FasL induced apoptosis ,as a resule of lead to pulmonary fibrosis pathogenesis were accepted by a lot of scholars. So interference Fas/FasL signal path, form pulmonary fibrosis, and its pathogenesis and pathological physiology and human disease process is basically the similar. In the past with bleomycin of pulmonary fibrosis model is made through direct induced lung inflammation in, cause pulmonary fibrosis, not only operation trival, and does not conform to the pathogenesis of pulmonary fibrosis and pathophysiological process. This research through the rat tail vein injection Fas antibody induced pulmonary fibrosis, in order to further study the pathogenesis of pulmonary fibrosis and to provide new treatment, to the pathogenesis of pulmonary fibrosis animal model, and through the subsequent experiments show this mechanism for pulmonary fibrosis, the research has important significance; DcR3 can antagonistic Fas/FasL apoptosis signaling pathways, this study also through the DcR3 intervention to Fas induced animal pulmonary fibrosis model , study the role of DcR3 , further confirm the theory.

肺纤维化模型是研究肺纤维化发病机制及药物治疗的先决条件。肺泡上皮细胞凋亡是肺纤维化形成的启动因素，导致上皮细胞凋亡的机制尚不清楚，其中Fas/FasL诱导的凋亡途径目前是很多学者认同的肺纤维化发生机制。因此干扰Fas/FasL信号通路，形成肺间质纤维化，其发病机制及病理生理与人的发病过程基本一致。以往用博莱霉素造的肺纤维化模型是通过直接诱导肺内炎症，导致肺纤维化，不仅操作繁琐，而且不符合肺纤维化的发病机制及病理生理过程。 本研究通过大鼠尾静脉注入Fas抗体诱导肺纤维化，为进一步研究肺纤维化的发病机制及治疗提供新的，符合人肺纤维化发病机制动物模型，并且通过后续实验证明这一机制，对肺间质纤维化的研究具有重要意义；DcR3可以拮抗Fas/FasL凋亡信号途径，因此本研究还通过DcR3对Fas诱导的动物肺纤维化模型的干预，探讨DcR3在Fas抗体诱导的肺纤维化发生发展的作用，进一步证实该理论。

肺纤维化模型是研究肺纤维化发病机制，并给予药物治疗的先决条件。肺泡上皮细胞的凋亡是肺纤维化形成的早期阶段，也是启动因素，导致上皮细胞凋亡的因素有很多，其中Fas/FasL诱导的凋亡途径目前是比较认同的肺纤维化发生发展的机制。因此干扰Fas/FasL通路，形成肺间质纤维化，其发病机制及病理生理与人的发病过程基本一致。.本研究通过对大鼠静脉注入Fas抗体诱导肺纤维化的模型建立新的肺纤维化动物模型，从而为进一步研究肺纤维化的发病机制及治疗提供新的更接近发病机制动物模型。DcR3可以拮抗Fas/FasL凋亡信号途径，因此本研究通过在此肺纤维化动物模型体内注射DcR3，研究DcR3在抗Fas抗体诱导的肺纤维化发生发展中的作用机制，观察DcR3抗肺泡上皮细胞凋亡及控制或减轻肺纤维化的作用，为研究肺纤维化发病机制奠定理论基础。