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纸质出版:2012
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曹姝,李少林,兰曦,王勇,邹冬玲,臧春宝,王颖.霉酚酸酯对小鼠肺纤维化的治疗作用[J].陆军军医大学学报(原第三军医大学学报),2012,34(24):2484-2488.
Cao Shu,Li Shaolin,Lan Xi,Wang Yong,Zou Dongling,Zang Chunbao,Wang Ying.Mycophenolate mofetil alleviates pulmonary fibrosis in mice[J].J Amry Med Univ (J Third Mil Med Univ),2012,34(24):2484-2488.
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(6 mg/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(20、60、100 mg/kg)MMF,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高剂量干预组较BLM模型组纤维化程度减轻,COLA1、COLA2 mRNA表达及TGF-β1蛋白表达明显降低(P0.01);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。
Objective To investigate the possible underlying mechanism of mycophenolate mofetil (MMF) in treating bleomycin (BLM)-induced pulmonary fibrosis in mice. Methods Thirty-six C57BL/6 mice were randomly divided into 6 groups (n=6 for each group)
including normal control group
MMF control group
BLM model group and MMF treatment groups at low
media and high doses. In 1 d after BLM (6 mg/kg) was intratracheally instilled to the mice from BLM model group and MMF treatment groups
MMF was given orally in the later groups at a dose of 20
60 and 100 mg/kg respectively once per day for 2 weeks. All mice were killed after the treatment
and their lung tissues were collected. Pulmonary fibrosis was evaluated by Ashcroft score after HE and masson trichrome staining. The expression of collagen 1 (COLA1) and COLA2 at mRNA levels was determined by RT-PCR. TGF-β1 protein was analyzed by immunohistochemistry. Results BLM-induced pulmonary fibrosis model was successfully constructed. High dose MMF treatment resulted in significant attenuated fibrosis
lower expression of COLA and COLA2 at mRNA level
and decreased TGF-β1 protein (P0.01) when compared with BLM group. No statistic difference was found between the other MMF treatment groups and BLM model groups
MMF control group and normal control group (P0.05). Conclusion MMF significantly attenuates BLM-induce pulmonary fibrosis in mice
which may be due to its inhibition of TGF-β1 expression.
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