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霉酚酸酯对小鼠肺纤维化的治疗作用
 

【作者】 曹姝； 李少林； 兰曦； 王勇； 邹冬玲； 臧春宝； 王颖；

【Author】 Cao Shu, Lan Xi, Wang Yong, Zou Dongling, Zang Chunbao, Wang Ying(Department of Radiology, Chongqing Medical University, Chongqing, 400016,China)

【机构】 重庆医科大学放射医学教研室；

【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、100mg/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、COLA2mRNA表达及TGF-β1蛋白表达明显降低(P<0.01)。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(P>0.05)。结论 ... 更多还原

【Abstract】 Objective To probe into the mechanism of mycophenolate mofetil(MMF) in treating bleomycin(BLM)-induced pulmonary fibrosis of mice. Methods 36 mice were randomly divided into 6 groups(6 mice in each group), including normal control group, MMF control group, BLM model group and MMF treatment groups which were consist of low, media and high dose. One day after intratracheally instilled BLM(6mg/kg) which was dissolved in saline in BLM model group and MMF treatment groups, MMF was given orally in MMF treatment groups(20,60,100 mg/kg) once daily for two weeks. All mice were killed two weeks later, and lung tissues were collected for the following experiments. Pulmonary fibrosis was evaluated by Ashcroft score in HE and masson trichrome stain. The expression of COLA1 and COLA2 mRNA were determined by RT-PCR. TGF-β1 protein were analyzed by immunohistochemistry. Results BLM-induced pulmonary fibrosis model was successfully constructed. The degree of fibrosis, expression of COLA,COLA2 mRNA and TGF-β1 protein(P<0.01) in high dose MMF treatment group decreased compared with BLM group. No statistic differences were found between the other MMF treatment groups and BLM model groups, MMF control group and normal control group(P>0.05). Conclusion MMF significantly attenuates BLM-induce pulmonary fibrosis in mice, which may be implicated in inhibition of TGF-β1 expression

霉酚酸酯: 霉酚酸的2-乙基酯类衍生物。在体内脱酯化后形成具有免疫抑制活性的代谢产物霉酚酸(MPA)，后者通过抑制鸟嘌呤合成，选择性阻断Ｔ和Ｂ细胞增殖，对移植排异和自身免疫病均有显著疗效，且不良反应较少。