發(fā)布時(shí)間：2018-06-02 04:26

  本文選題：霉酚酸酯 + 博萊霉素�。� 參考：《重慶醫(yī)科大學(xué)》2013年碩士論文

【摘要】：目的初步探討霉酚酸酯（Mycophenolate mofetil, MMF）在博萊霉素（bleomycin,BLM）誘導(dǎo)的小鼠肺纖維化模型中的保護(hù)作用及分子機(jī)制。 方法將36只C57BL/6小鼠隨機(jī)分為6組，每組6只，分別為正常對(duì)照組、MMF對(duì)照組、BLM模型組、MMF干預(yù)組（分為低、中、高劑量組）；于實(shí)驗(yàn)第1天將BLM模型組、MMF干預(yù)組經(jīng)氣管注入BLM（6mg/kg溶于50μl生理鹽水）；從實(shí)驗(yàn)第2天開始對(duì)MMF干預(yù)組分別給予低、中、高劑量的MMF(20，60，100mg/kg)，MMF對(duì)照組給予100mg/kg；于實(shí)驗(yàn)第16天處死所有小鼠，，收集小鼠肺臟標(biāo)本；HE, Masson染色從組織形態(tài)學(xué)上觀察肺組織纖維化病變情況，Aschcroft法進(jìn)行肺纖維化評(píng)分； RT-PCR檢測(cè)各組肺組織中轉(zhuǎn)化生長(zhǎng)因子-β1（transforming growth factorβ1, TGF-β1）、COL1A1及COL1A2的基因表達(dá)水平；利用免疫組化法、Western blot檢測(cè)各組肺組織中TGF-β1的蛋白表達(dá)情況。 結(jié)果BLM誘導(dǎo)的小鼠肺纖維化模型構(gòu)建成功，MMF高劑量干預(yù)組與BLM模型組比較，前者的纖維化程度減輕，在mRNA水平降基金來(lái)源：重慶市科委資助項(xiàng)目（CSTC2009B5059）低了COL1A1及COL1A2的表達(dá)(P0.01)，TGF-β1在轉(zhuǎn)錄及蛋白水平明顯降低（P0.05）。而低劑量組和中劑量組與BLM模型組間、MMF對(duì)照組與正常對(duì)照組間差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。 結(jié)論MMF能有效減輕BLM誘導(dǎo)的小鼠肺纖維化病變，并在轉(zhuǎn)錄水平抑制I型膠原的基因表達(dá)，其機(jī)制可能與下調(diào)促纖維化細(xì)胞因子TGF-β1相關(guān)。
[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.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2013
【分類號(hào)】：R563.8

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相關(guān)期刊論文 前2條

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本文編號(hào)：1967384