霉酚酸酯对小鼠肺纤维化的治疗作用-第三军医大学学报.DOCVIP

霉酚酸酯对小鼠肺纤维化的治疗作用 曹 姝，李少林，兰 曦，王 勇，邹冬玲，臧春宝，王 颖[基金项目] 重庆市科委资助项目（CSTC2009B5059）[通信作者] 王 颖，电话：（023E-mail: [基金项目] 重庆市科委资助项目（CSTC2009B5059） [通信作者] 王 颖，电话：（023E-mail: wangying_cq@ [摘要] 目的 探讨霉酚酸酯（mycophenolate mofetil,MMF）对博莱霉素（bleomycin,BLM）诱导的小鼠肺纤维化模型的治疗作用。方法 将36只C57BL/6小鼠完全随机分为6组：正常对照组、MMF对照组、BLM模型组及MMF干预组（分为低、中、高剂量组），每组6只。实验第1天BLM模型组、MMF干预组经气管注入BLM（6mg/kg），正常对照组、MMF对照组则注入等量生理盐水。从实验第2天开始MMF干预组分别给予低、中、高剂量MMF(20、60、100 mg/kg)，2周后处死所有小鼠，收集肺脏标本；HE、Masson染色在组织形态学上观察肺纤维化病变情况，Aschcroft法评分；RT-PCR检测COLA1及COLA2的mRNA表达水平；免疫组化法检测肺组织TGF-β1的蛋白表达。结果 BLM诱导的肺纤维化模型构建成功；MMF高剂量干预组与BLM模型组比较，前者的纤维化程度减轻，COLA1、COLA2 mRNA表达及TGF-β1蛋白表达明显降低（P0.01）。而低、中剂量组与BLM模型组间、MMF对照组与正常对照组间差异无统计学意义(P0.05)。结论 MMF能有效减轻BLM诱导的肺纤维化病变，其机制可能与下调促纤维化细胞因子TGF-β1相关。 [关键词] 霉酚酸酯；博莱霉素；肺纤维化；转化生长因子-β1；Ⅰ型胶原 [中图法分类号] [文献标志码] A Mechanism of mMycophenolate mofetil alleviateson treating pulmonary fibrosis in mice models Cao Shu, Li Shaolin, Lan Xi, Wang Yong, Zou Dongling, Zang Chunbao, Wang Ying (Department of Radiology, College of Preventive Medicine, Chongqing Medical University, Chongqing, 400016 [Abstract] Objective To investigate the possible underlying probe into the mechanism of mycophenolate mofetil (MMF) in treating bleomycin (BLM)-induced pulmonary fibrosis ofin mice. Methods 36Thirty-six C57BL/6 mice were randomly divided into 6 groups (n=6 mice infor each group), including normal control group, MMF control group, BLM model group and MMF treatment groups at which were consist of low, media and high doses. In 1 One day after BLM (6 mg/kg) was intratracheally instilled BLM(6mg/kg) whito the mice from ch was dissolved in saline in BLM model group and MMF treatment groups, MMF was given orally in the later MMF treatment groups at a dose of (20, 60 and ,100 mg/kg) respectively once dailyper day for two 2 weeks. All mice were killed after the treatmenttwo weeks later, and their lung tissues were collected for the following experiments. Pulmonary fibrosis was evaluated