探讨松弛素（relaxin）对矽尘致肺纤维化的拮抗作用及机制，可能开启矽肺防治研究的新方向。本研究项目的结果包括两方面内容：（1）Relaxin、肺纤维化相关因子基因表达在石英尘诱导大鼠矽肺过程中肺组织的演变规律、相互关系；（2）Relaxin 体外对石英尘致纤维化的拮抗作用和机制。.在第一方面，主要阐明了石英尘诱导大鼠矽肺过程中：肺组织Relaxin和其受体LGR7蛋白细胞定位的改变（由以Ⅰ型肺泡细胞为主变为以Ⅰ型肺泡细胞、巨嗜细胞为主）；Relaxin、LGR7、Collagen type-I、TGF-β1、MMPs和TIMPs mRNA表达水平的时间变化趋势。在第二方面，主要证实了：Relaxin 体外对石英尘、TGF-β1 致人胚肺成纤维细胞MRC-5或HFL-1增殖和胶原生成的抑制作用,对人血单核细胞THP-1 TGF-β1 mRNA表达的抑制，对MRC-5细胞MMPs活性的诱导；在THP-1细胞中和在实验性矽肺肺组织中，石英尘诱导的Relaxin、LGR7、TGF-β1和MMPs mRNA表达的时间变化模式一致。

A study of antagonism and mechanism of relaxin against silica-induced pulmonary fibrosis may open new perspectives for prevention and treatment of silicosis. The results of this research program include two contents: (1) the relationship between changes in gene expression of relaxin and pulmonary fibrosis-related factors in rat lung tissue during experimental silicotic induced by crystalline silica; (2) anti-fibrotic properties of relaxin in in vitro models of fibrosis induced by crystalline silica. .First kind of results is mainly about the change in the target protein cellular location and in target mRNA profiles with the development of experimental silicosis induced by crystalline silica. The location of relaxin and its receptor proteins (LGR7) changed from being primaily located in pulmonary alveolar type I cells to being mostly found in pulmonary alveolar type I cells and alveolar macrophages. The tendencies in the changes of gene expression of Relaxin, LGR7, Collagen type-I, TGF-β1, MMPS and TIMPs in lung tissue were elucidated.Second kind of results mainly confirmed that Relaxin could inhibit human fetal lung fibroblasts (MRC-5 cells or HFL-1 cells) proliferation and collagen production, which were induced by crystalline silica or TGF-β1 in vitro, and mRNA expression of TGF-β1 in human monocytic-leukemia cells (THP-1), and increase MMPs activity in MRC -5 cells. In addition, the mRNA expression patterns of Relaxin, LGR7, TGF-β1 and MMPs induced by crystalline silica in THP-1 cells is consistent with that in lung tissue of experimental silicosis induced by crystalline silica.

探讨松弛素（relaxin）对矽尘致肺纤维化的拮抗作用及机制，可能开启矽肺防治研究的新方向。本研究项目的结果包括两方面内容：（1）Relaxin、肺纤维化相关因子基因表达在石英尘诱导大鼠矽肺过程中肺组织的演变规律、相互关系；（2）Relaxin 体外对石英尘致纤维化的拮抗作用和机制。在第一方面，主要阐明了石英尘诱导大鼠矽肺过程中：肺组织Relaxin和其受体LGR7蛋白细胞定位的改变（由以Ⅰ型肺泡细胞为主变为以Ⅰ型肺泡细胞、巨嗜细胞为主）；Relaxin、LGR7、Collagen type-I、TGF-β1、MMPs和TIMPs mRNA表达水平的时间变化趋势。在第二方面，主要证实了：Relaxin 体外对石英尘、TGF-β1 致人胚肺成纤维细胞MRC-5或HFL-1增殖和胶原生成的抑制作用,对人血单核细胞THP-1 TGF-β1 mRNA表达的抑制，对MRC-5细胞MMPs活性的诱导；在THP-1细胞中和在实验性矽肺肺组织中，石英尘诱导的Relaxin、LGR7、TGF-β1和MMPs mRNA表达的时间变化模式一致。