颗粒蛋白前体在博来霉素致肺纤维化小鼠中的表达

Progranulin expression in bleomycin⁃induced pulmonary fibrosis in mice

目的:探讨颗粒蛋白前体(PGRN)在博来霉素致肺纤维化小鼠肺组织中的表达。方法:选取C57BL/6小鼠36只,随机分为3组,博来霉素模型组向气管内灌注博来霉素(5 mg/kg)后第14、28天分批处死小鼠,生理盐水对照组注入等量的生理盐水。肺组织采用HE染色和Masson染色观察小鼠肺组织炎症和纤维化情况,以免疫组化法检测PGRN在肺组织中的分布和表达,蛋白印迹法检测PGRN在小鼠肺组织中的蛋白表达水平。结果:光镜下观察发现,生理盐水对照组小鼠肺组织结构完整,少量炎症细胞浸润;博来霉素组小鼠肺组织结构破坏,炎症细胞浸润,呈弥漫性肺纤维化改变。免疫组化检测可见博来霉素组小鼠PGRN在肺泡巨噬细胞和肺泡上皮细胞中的阳性率明显高于生理盐水对照组,肺组织中PGRN蛋白表达水平明显升高(P<0.05)。结论:PGRN可能参与了博来霉素致小鼠肺纤维化的过程。

Objective:To examine the expression of progranulin(PGRN)in the lungs of mice with bleomycin-induced pulmonary fibrosis.Methods:A total of 36 C57BL/6 mice were selected and randomly divided into three groups.The bleomycin group underwent intra-tracheal administration of bleomycin(5 mg/kg)and the control group received the same volume of normal saline.Both groups of mice were sacrificed,in batches,on days 14 and 28 following intervention.Lung tissue was examined with hemotoxalin and eosin and Masson’s trichome stains to demonstrate pulmonary inflammation and fibrosis in the mice.The distribution and expression of progranulin in lung tissue were examined using immunohistochemistry staining.Levels of PGRN protein expression in murine lung tissue were determined by Western blot.Results:Microscopic examination revealed that lung tissue in saline control mice was intact with minor inflammatory cell infiltration.However,lung tissue in bleomycin treated mice was damaged,with inflammatory cell infiltration and diffuse pulmonary fibrosis.Immunohistochemical staining showed a statistically significantly greater positive rate of PGRN in alveolar macrophages and in alveolar epithelial cells in the bleomycin group compared to the saline controls,and the pulmonary PGRN protein expression was significantly increased(P<0.05).Conclusion:PGRN may be involved in bleomycin-induced lung fibrosis in mice.