Ma Wan-Li, Ye Hong, Tao Xiao-Nan, Xin Jian-Bao
Pulmonary Laboratory of Ministry of Health of China, Department of Respiratory Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China;Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China;E?mail:
Sheng Li Xue Bao. 2005 Aug 25;57(4):493-7.
To investigate the role of found in inflammatory zone 1 (FIZZ1) protein in the pathogenesis of experimental pulmonary fibrosis, 48 male Sprague-Dawley rats were randomly divided into two groups, the pulmonary fibrosis group and the control group. Rat pulmonary fibrosis was reproduced by an intratracheal injection of bleomycin (5 mg/kg body weight). Normal saline (1 ml/kg body weight) was given intratracheally injection in the control group. There were 24 rats in each group, and 6 animals were separately killed on the 7th, 14th, 21th and 28th day after treated with bleomycin or normal saline. Then the following tests were undertaken: (1) HE and Masson staining of lung section;(2) Determination of lung tissue hydroxyproline (HYP);(3) Immunohistochemical staining of protein of FIZZ1 in the lung;(4) In situ hybridization of FIZZ1 mRNA in the lung. The results showed: (1) There were full of inflammatory cells in the lung, the interval of alveoli enlarged and many alveolar spaces disappeared on the 7th day after treated with bleomycin in the fibrosis group. Collagen began to proliferate after 14 d. The pulmonary fibrosis was stably established on the 28th day, full of green fibers in the Masson staining of lung section. (2) The expression of FIZZ1 protein in the lung increased after 7 d in bleomycin-treated animals (3.013+/-0.326 vs 0.473+/-0.056, P<0.01 vs control), but was slightly decreased on the 14th day (2.124+/-0.197) and expensively decreased on the 21st day (1.760+/-0.105) and the 28th day (0.691+/-0.081). (3) The expression of FIZZ1 mRNA in the lung also increased after 7 d by treated with bleomycin (3.795+/-0.338 vs 0.678+/-0.087, P<0.01 vs control), but decreased on the 14th day (1.276+/-0.104) and further decreased on the 28th day (0.896+/-0.084). The expression of FIZZ1 protein and mRNA in fibrosis group was higher than that in the control group (P<0.05 or P<0.01). The results suggest that FIZZ1 protein and FIZZ1 mRNA are dynamically changed in the lung with experimental pulmonary fibrosis, which may contribute to the pathogenesis of pulmonary fibrosis.
为探讨炎症区域1发现蛋白(FIZZ1)在实验性肺纤维化发病机制中的作用,将48只雄性Sprague-Dawley大鼠随机分为两组,即肺纤维化组和对照组。通过气管内注射博来霉素(5mg/kg体重)复制大鼠肺纤维化模型。对照组气管内注射生理盐水(1ml/kg体重)。每组24只大鼠,在给予博来霉素或生理盐水处理后的第7、14、21和28天分别处死6只动物。然后进行以下检测:(1)肺组织切片的HE和Masson染色;(2)肺组织羟脯氨酸(HYP)测定;(3)肺组织中FIZZ1蛋白的免疫组织化学染色;(4)肺组织中FIZZ1 mRNA的原位杂交。结果显示:(1)纤维化组在给予博来霉素处理后第7天,肺内充满炎性细胞,肺泡间隔增宽,许多肺泡腔消失。14天后胶原开始增生。第28天肺纤维化稳定形成,肺组织切片Masson染色可见大量绿色纤维。(2)博来霉素处理动物肺内FIZZ1蛋白表达在7天后升高(3.013±0.326 vs 0.473±0.056,与对照组相比P<0.01),但在第14天略有下降(2.124±0.197),在第21天(1.760±0.105)和第28天(0.691±0.081)显著下降。(3)博来霉素处理后肺内FIZZ1 mRNA表达在7天后也升高(3.795±0.338 vs 0.678±0.087,与对照组相比P<0.01),但在第14天下降(1.276±0.104),在第28天进一步下降(0.896±0.084)。纤维化组FIZZ1蛋白和mRNA的表达高于对照组(P<0.05或P<0.01)。结果提示,在实验性肺纤维化过程中,肺内FIZZ1蛋白和FIZZ1 mRNA呈动态变化,这可能与肺纤维化的发病机制有关。