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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组织中转化生长因子-β1(transforming growth factor-β1,TGF-β1)表达的影响。方法将C57BL/6小鼠随机分为6组:正常对照组、MMF对照组、BLM模型组、MMF低(20 mg/kg)、中(60 mg/kg)、高(100 mg/kg)剂量干预组,每组6只。BLM模型组和MMF 3个干预组经气管注入BLM(6 mg/kg),正常对照组和MMF对照组注入等量无菌生理盐水;次日按MMF对照组和MMF干预低、中、高剂量组小鼠体重计算MMF给药量,灌胃小鼠,每日1次,连续14 d,正常对照组和BLM模型组用等体积的双蒸水灌胃。灌胃第16天采集小鼠肺脏标本,经HE、Masson染色,从组织形态学上观察肺组织纤维化情况并进行Aschcroft评分;RT-PCR法检测小鼠肺组织中TGF-β1基因mRNA的转录水平;Western blot法检测小鼠肺组织中TGF-β1蛋白的表达水平。结果 BLM诱导的小鼠肺纤维化改变显著,Ashcroft评分较正常对照组显著增高(P<0.01),表明小鼠肺纤维化模型构建成功;MMF高剂量干预组肺组织损伤减轻,炎细胞浸润及胶原沉积减少,Ashcroft评分显著降低(P=0.000)。MMF高剂量干预组与BLM模型组比较,TGF-β1基因mRNA的转录水平及蛋白的表达水平均明显减低(P<0.05);而MMF低、中剂量干预组与BLM模型组之间、MMF对照组与正常对照组之间,差异均无统计学意义(P>0.05)。结论高剂量的MMF(100 mg/kg)可抑制BLM诱导的肺纤维化小鼠肺组织中TGF-β1基因mRNA的转录水平及蛋白表达水平,有望成为治疗肺纤维化的理想药物。
Objective To investigate the effect of mycophenolate mofetil (MMF) on the expression of transforming growth factor-β1 (TGF-β1) in pulmonary fibrosis induced by bleomycin (BLM) in mice. . Methods C57BL / 6 mice were randomly divided into 6 groups: normal control group, MMF control group, BLM model group, MMF low (20 mg / kg) Intervention group, 6 rats in each group. BLM model group and MMF intervention group were injected with BLM (6 mg / kg) intratracheal intratracheal intratracheal intratracheal instillation of normal saline and MMF control group. The next day, MMF control group and MMF intervention group were given low, medium and high dose The mice were weighed and the MMF dose was calculated. The mice were given intragastrically once a day for 14 consecutive days. The normal control group and the BLM model group were intragastrically administered with an equal volume of double distilled water. The lungs of mice were collected on the 16th day after gavage, stained with HE and Masson, and the lung fibrosis was observed by histomorphology and Aschcroft score. The transcription of TGF-β1 mRNA was detected by RT-PCR Western blot was used to detect the expression of TGF-β1 protein in lung tissue of mice. Results The pulmonary fibrosis induced by BLM in mice was significantly changed, and the Ashcroft score was significantly higher than that in the normal control group (P <0.01), indicating that the model of pulmonary fibrosis was established successfully in mice treated with BLM. The lung injury, inflammatory cell infiltration, Decreased collagen deposition, Ashcroft score was significantly reduced (P = 0.000). MMF high-dose intervention group and BLM model group, TGF-β1 mRNA and protein expression levels were significantly lower (P <0.05), while MMF low and medium dose intervention group and BLM model group, MMF control There was no significant difference between the two groups (P> 0.05). Conclusion High dose of MMF (100 mg / kg) can inhibit the mRNA and protein expression of TGF-β1 in the lung of BLM-induced pulmonary fibrosis mice and is expected to become an ideal drug for the treatment of pulmonary fibrosis.