霉酚酸酯对博莱霉素诱导的小鼠肺纤维化的保护作用及分子机制研究

发布时间：2018-06-02 04:26

本文选题：霉酚酸酯 + 博莱霉素　；参考：《重庆医科大学》2013年硕士论文

【摘要】：目的初步探讨霉酚酸酯（Mycophenolate mofetil, MMF）在博莱霉素（bleomycin,BLM）诱导的小鼠肺纤维化模型中的保护作用及分子机制。方法将36只C57BL/6小鼠随机分为6组，每组6只，分别为正常对照组、MMF对照组、BLM模型组、MMF干预组（分为低、中、高剂量组）；于实验第1天将BLM模型组、MMF干预组经气管注入BLM（6mg/kg溶于50μl生理盐水）；从实验第2天开始对MMF干预组分别给予低、中、高剂量的MMF(20，60，100mg/kg)，MMF对照组给予100mg/kg；于实验第16天处死所有小鼠，，收集小鼠肺脏标本；HE, Masson染色从组织形态学上观察肺组织纤维化病变情况，Aschcroft法进行肺纤维化评分； RT-PCR检测各组肺组织中转化生长因子-β1（transforming growth factorβ1, TGF-β1）、COL1A1及COL1A2的基因表达水平；利用免疫组化法、Western blot检测各组肺组织中TGF-β1的蛋白表达情况。结果BLM诱导的小鼠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，在mRNA水平降基金来源：重庆市科委资助项目（CSTC2009B5059）低了COL1A1及COL1A2的表达(P0.01)，TGF-β1在转录及蛋白水平明显降低（P0.05）。而低剂量组和中剂量组与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诱导的小鼠肺纤维化病变，并在转录水平抑制I型胶原的基因表达，其机制可能与下调促纤维化细胞因子TGF-β1相关。
[Abstract]:Objective to investigate the protective effect and molecular mechanism of mycophenolate mofetil (MMF) on bleomycin induced pulmonary fibrosis in mice. Methods 36 C57BL/6 mice were randomly divided into 6 groups, 6 in each group. On the first day of the experiment, the BLM model group was injected with BLM(6mg/kg dissolved in 50 渭 l normal saline solution through trachea. From the second day of the experiment, the rats in the MMF intervention group were given low and middle, respectively. The control group was given 100 mg / kg of MMF, and all the mice were killed on the 16th day of the experiment. The lung specimens of mice were collected. The pathological changes of pulmonary fibrosis were observed by Masson staining. The pulmonary fibrosis score was evaluated by Aschcroft method, and the expression levels of transforming growth factor-尾 1(transforming growth factor 尾 1, TGF- 尾 1, COL1A1 and COL1A2 in lung tissues were detected by RT-PCR. The expression of TGF- 尾 1 protein in lung tissue was detected by immunohistochemistry and Western blot. Results compared with the model group of BLM, the degree of pulmonary fibrosis in the high dose intervention group of BLM was reduced compared with that in the model group of BLM, and the model of pulmonary fibrosis in mice induced by BLM was established successfully. CSTC2009B5059, a project funded by Chongqing Science and Technology Commission, decreased the expression of COL1A1 and COL1A2, and the expression of P0.01TGF- 尾 1 significantly decreased the transcription and protein levels of P0.05A. However, there was no significant difference between the low dose group and the middle dose group and the BLM model group between the control group and the normal control group (P 0.05). Conclusion MMF can attenuate the pathological changes of pulmonary fibrosis induced by BLM in mice and inhibit the gene expression of type I collagen at the transcriptional level. The mechanism may be related to the down-regulation of TGF- 尾 1.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R563.8

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