TGF-β3通过调控MMP-9/TIMP-1比例和VEGF表达延缓小鼠放射性肺纤维化  

Transforming growth factor 3 attenuates the development of radiation-induced pulmonary fibrosis in mice by regulating the ratio of MMP-9/TIMP-1 and expression of VEGF

作　　者：杨长爽 徐龙[2] 杨陟华[2] 梁鑫[1,2] 胡蝶[2] 潘秀颉[2] 朱茂祥[1,2] 周平坤[1,2] YANG Chang-shuang XU Long YANG Zhi-hua LIANG Xin HU Die PAN Xiu-jie ZHU Mao-xiang ZHOU Ping-kun(Graduate School, Anhui Medical University, Hefei 230032, China Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China)

机构地区：[1]安徽医科大学研究生院,合肥230032 [2]军事医学科学院放射与辐射医学研究所,北京100850

出　　处：《军事医学》2017年第2期81-85,共5页Military Medical Sciences

基　　金：国家自然科学基金资助项目(81472910);国家科技支撑计划资助项目(2013BAH02B00)

摘　　要：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 in lungs of mice after 60 Co γ-ray irradiation, and to explore the regulation mechanism of transforming growth factor-β3（TGF-β3） on radiation pulmonary fibrosis. Methods A total of 180 C57BL/6 female mice were randomly divided into control group, irradiation group and TGF-β3 group. The irradiation and TGF-β3 groups were treated with 60Co γ-ray for 20 Gy thoracic irradiation. After irradiation, 0.5 ml 0.9% NS and TGF-β3 （ 1 μg/ kg） were injected intraperitoneally once every 7 days. The body mass and lung mass of the mice were observed at 1 month, 3 months and 6 months after irradiation. Routine pathological examination and Masson trichrome staining were performed. The expression of matrix metalloproteinase （MMP） -9 and tissue inhibitor of metalloproteinases （TIMP） -1 in lung tissue was detected by immunohistochemistry. And the vascular endothelial growth factor （VEGF） content in the bronchoalveolar lavage fluid （BALF） was measured. Results The body mass of all the three groups increased gradually, while the body mass of irradiation and TGF-β3 groups decreased significantly compared with the control group. The lung mass of mice in irradiation and TGF-β3 groups at 6 months after irradiation, and the lung mass of the TGF-β3 group were higher than in the irradiation group. Pathological sections after HE staining and Masson trichrome staining results showed that compared with the control group, 6 months after irradiation, the lung tissue of irradiated mice showed significant fibrosis, and the degree of pulmonary fibrosis in TGF-β3 group was significantly less than that in irradiation group. The expression of MMP-9/TIMP-1 in lung tissue was significantly higher than that in the control group. At the same time, the expression level of VEGF in irradiation group was significantly higher than that in control group, while it was significantly lower in TGF-β3 group than that in control group. The expression level of VEGF group after 3 months was similar to

关 键 词：转化生长因子-Β3 小鼠 放射性肺纤维化 基质金属蛋白酶-9/基质金属蛋白酶组织抑制剂-1 血管内皮 

分 类 号：R730.55[医药卫生—肿瘤]