百草枯致小鼠肺间质纤维化过程中转化生长因子-β1的表达

The changes of transforming growth factor -β1 in pulmonary fibrosis induced by paraquat in mice

目的用免疫组织化学的方法观察百草枯（PQ）致肺间质纤维化过程中转化生长因子-β1（TGF-β1）的表达。方法58只雄性C57BL／6J小鼠随机（随机数字法）分组。实验组48只，通过腹腔注射PQ（10mg／kg）建立小鼠肺间质纤维化模型；对照组10只，腹腔注射等量生理盐水。实验组染毒后2，5，7，14d和对照组7d时小鼠分别被处死，留取肺组织标本。标本进一步进行HE染色和TGF-β1的免疫组化研究，并进行TGF-β1的积分光密度（iOD）分析，两组间的数据比较采用成组t检验。结果PQ致肺纤维化过程中，巨噬细胞中TGF-β1表达显著增加。随着纤维化进程的进展，TGF-β1染色阳性主要见于浸润的巨噬细胞和中性粒细胞的胞浆中。染毒后14d，除了巨噬细胞外，TGF-β1染色阳性也见于成纤维细胞灶中的成纤维细胞和肌成纤维细胞。与对照组相比，实验组各时间点TGF-β1的积分光密度在纤维化开始后明显增加（P〈0．01）并呈上升趋势。结论在PQ致肺间质纤维化过程中，TGF-β1的表达显著增加并对肺纤维化的发生发展具有重要的作用。

Objective To study the changes of transforming growth factor-β1（TGF-β1） in pulmonary fibrosis induced by paraquat （PQ） with immunohistochemistry method. Methods A total of 58 C57BL/6J male mice were randomly （random number） divided into the experimental group and control group. Pulmonary fibrosis was induced by intra-peritoneal injection of PQ in dose of 10 mg/kg into the mice of experimental group （n = 48 ）, while physiological saline was used instead in mice of control group （n = 10）. The mice of experimental group were sacrificed 2, 5, 7 and 14 days after PQ poisoning and the mice of control group were sacrificed on the 7th day after saline administration. Lungs of mice were taken and histological changes in lungs were evaluated by haematoxylin-eosin stain, and TGF-β1 was determined with immunohistochemistry method. The integrated optical density （iOD） value of TGF-β1 was measured and analyzed. Results The TGF-β1 was markedly increased in macrophages during the genesis of pulmonary fibrosis induced by PQ. As the course of fibrosis progressed, the positive staining of TGF-β1 was mainly seen in macrophages and neutrophil cytoplasm. On the 14th day after PQ poisoning, TGF-β1-positive cells were also detected in the fibroblast and myo-fibroblast inside the fibroblastic loci. Compared with the control group, the iOD value of TGF-β1 increased in experimental group （P 〈 0. 01 ） and it gradually upgraded during the course of fibrosis. Conclusions The TGF-β1 significantly increased during the course of pulmonary fibrosis induced by PQ and played an important role in the pathogenesis of the disease.