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中图分类号：R 563.1

实验性肺纤维化大鼠发病过程中肺组织FIZZ1的动态变化

马万里¹，叶红²，陶晓南¹，辛建保¹

¹华中科技大学同济医学院附属协和医院呼吸内科，卫生部呼吸系疾病重点实验室，武汉430022； ²华中科技大学同济医学院病理生理系，武汉430030

摘 要：应用博莱霉素（5 mg/kg体重）气管内注入复制实验性大鼠肺纤维化模型，采用HE染色、Masson三联染色、羟脯氨酸含量测定、免疫组织化学染色、原位杂交等方法，观察实验性大鼠肺纤维化的发病过程及其肺组织中FIZZ1（found in inflammatory zone 1）蛋白、mRNA表达水平的动态变化，以探讨FIZZ1在肺纤维化发病中的作用。结果显示：(1) 实验性大鼠肺纤维化发病过程中，呈现典型的肺泡炎（7 d）、纤维组织增生（14～21 d）及稳定的肺纤维化（28 d）等表现；(2) FIZZ1蛋白在正常肺组织表达较弱，在肺纤维化组7 d时表达明显增强，14 d时较7 d时有所减弱，21 及28 d明显减弱；(3) FIZZ1 mRNA在正常肺组织中表达较弱，在肺纤维化组7 d时表达明显增强，14 d时开始减弱，21 d及28 d明显减弱，但仍强于正常组。上述结果提示，FIZZ1在实验性大鼠肺纤维化发病过程中呈现明显的动态变化，并可能参与了肺纤维化的发生。

关键词：肺；纤维化；FIZZ1

Dynamic changes of found in inflammatory zone 1 protein and mRNA expression in the lung with experimental pulmonary fibrosis of the rat

MA Wan-Li¹, YE Hong^2,*, TAO Xiao-Nan¹, XIN Jian-Bao¹

¹Department of Respiratory Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Pulmonary Laboratory of Ministry of Health of China, Wuhan 430022, China; ²Department of Pathophysiology, Tongji Medical College, Hua Zhong University of Science and Technology, Wuhan 430030, China

Abstract：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 (5mg/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 at 7, 14, 21 and 28 d 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 at the 7^th day after treated with bleomycin in the fibrosis group. Collagen began to proliferate after 14 d. The pulmonary fibrosis was stably established at the 28^th 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 at the 14^th day (2.124±0.197) and expensively decreased at the 21^st day (1.760±0.105) and the 28^th 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 at 14^th day (1.276±0.104) and further decreased at the 28^th 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.

Key words: pulmonary; fibrosis; found in inflammatory zone 1 (FIZZ1)