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目的观察经~(60)Coγ射线全胸照射后小鼠肺脏的改变,探究转化生长因子-β3(transforming growth factor-β3,TGF-β3)对放射性肺纤维化的相关调节机制。方法 180只C57BL/6雌性小鼠随机分为对照组、照射组和TGF-β3组。照射组和TGF-β3组经~(60)Coγ射线单次20 Gy胸部照射,照射后每7 d分别腹腔注射0.5 ml 0.9%生理盐水和TGF-β3(1μg/kg)1次。于照后1、3和6个月分别观察小鼠的体质量和肺质量,活杀后进行常规病理检查和Masson三色染色观察,免疫组织化学法检测肺组织中基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)和基质金属蛋白酶组织抑制剂-1(tissue inhibitor of metalloproteinases-1,TIMP-1)的表达,检测肺泡灌洗液(bronchoalveolar 1avage fluid,BALF)中血管内皮生长因子(vascular endothelial growth factor,VEGF)含量。结果经胸部照射后,3组小鼠体质量均逐渐升高,照射组和TGF-β3组小鼠体质量较对照组呈明显下降趋势;小鼠肺质量在照后3个月和6个月时照射组和TGF-β3组明显高于对照组,照后6个月时,TGF-β3组小鼠肺质量高于照射组。病理切片HE染色和Masson三色染色结果显示与对照组相比,照后6个月时,照射组小鼠肺组织结构有显著的纤维化病灶形成,而TGF-β3组肺组织纤维化发病程度与照射组相比病症明显减轻;免疫组化结果显示加入TGF-β3后,肺组织MMP-9/TIMP-1的比例显著升高,并随照后时间延长而进一步增强;同时照射组的VEGF表达水平在照后明显增高,而TGF-β3组较对照组相比显著降低,从3个月开始表达水平趋于和对照组相同。结论 TGF-β3可能通过调节肺内MMP-9/TIMP-1比例升高,降低肺内VEGP的表达水平,从而减轻或延缓小鼠放射性肺纤维化。
Objective To observe the changes of the lungs of mice exposed to ~ (60) Co γ-ray whole chest irradiation and to explore the regulatory mechanism of transforming growth factor-β3 (TGF-β3) on radiation-induced pulmonary fibrosis. Methods 180 C57BL / 6 female mice were randomly divided into control group, irradiation group and TGF-β3 group. The irradiated group and the TGF-β3 group were irradiated with 20 Gy of 60 Gy Coγ-ray and intraperitoneally injected with 0.5 ml 0.9% normal saline and TGF-β3 (1 μg / kg) every 7 days. The body weight and lung mass of the mice were observed at 1, 3 and 6 months after the irradiation respectively. The pathological examination and Masson trichrome staining were performed on the mice after death. Immunohistochemistry was used to detect the expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in bronchoalveolar 1avage fluid (BALF) vascular endothelial growth factor (VEGF) content. Results After thoracic irradiation, the body weight of three groups of mice increased gradually. The body weight of mice in the irradiation group and TGF-β3 group decreased significantly compared with the control group. The lung mass of mice in the three months and six months after irradiation At 6 months after irradiation, the lung mass of TGF-β3 group was higher than that of irradiation group when the irradiation group and TGF-β3 group were significantly higher than that of the control group. Pathological sections HE staining and Masson trichrome staining results showed that compared with the control group, 6 months after irradiation, the lung tissue of irradiated mice had significant fibrosis lesions, and TGF-β3 group, the incidence of pulmonary fibrosis Compared with the irradiation group, the symptoms were significantly reduced. The results of immunohistochemistry showed that the proportion of MMP-9 / TIMP-1 in lung tissue was significantly increased after TGF-β3 addition, and further enhanced with the prolongation of irradiation time. The expression of TGF-β3 was significantly higher in the control group than in the control group, and the expression level of TGF-β3 group was the same as that of the control group from the third month. Conclusion TGF-β3 may reduce or delay radiation-induced pulmonary fibrosis in mice by regulating the ratio of MMP-9 / TIMP-1 in the lung and decreasing the expression of VEGP in the lung.