本文選題：哮喘 + 肥胖��； 參考：《青島大學(xué)》2017年碩士論文

【摘要】：目的:探討TGF-β對(duì)肥胖哮喘小鼠氣道重塑的影響及吡非尼酮干預(yù)的作用。方法:將75只健康雌性C57BL/6J小鼠隨機(jī)均分為:對(duì)照組(A組)、肥胖組(B組)、肥胖哮喘組(C組)、布地奈德治療組(D組)、吡非尼酮治療組(E組)。肥胖組小鼠均采用高脂飲食誘導(dǎo)肥胖,其中C、D、E組小鼠采用卵白蛋白腹腔注射致敏聯(lián)合霧化吸入激發(fā)的方法構(gòu)建哮喘模型,對(duì)照組小鼠均采用普通飼料飼養(yǎng),同期給予生理鹽水致敏激發(fā)。布地奈德治療組小鼠給予布地奈德懸液霧化吸入(0.5mg/ml,30min/次,qd),吡非尼酮治療組給以吡非尼酮(300mg/kg)飲水干預(yù),其余組給予正常飲水。治療4周后,收集小鼠支氣管肺泡灌洗液(BALF)進(jìn)行細(xì)胞計(jì)數(shù)及分類。采用HE、PAS、Masson染色觀察肺組織病理切片的氣道炎癥、氣道重塑及氣道粘液分泌情況。采用ELISA法測(cè)定血清中轉(zhuǎn)化生長(zhǎng)因子β(TGF-β)濃度,取右肺組織用Westernblot檢測(cè)TGF-β的表達(dá)變化情況。應(yīng)用計(jì)算機(jī)圖像分析軟件技術(shù)測(cè)定氣管壁總面積(WAt)、氣道平滑肌面積(WAm)和管腔基底膜周長(zhǎng)(Pbm)。結(jié)果:試驗(yàn)過程中,肥胖組小鼠體質(zhì)量明顯高于空白對(duì)照組(P0.05)。致敏激發(fā)過程中,哮喘各組小鼠均有不同程度的哮喘急性發(fā)作表現(xiàn)。至小鼠干預(yù)結(jié)束時(shí),各組小鼠均無死亡。肥胖哮喘組小鼠BALF中白細(xì)胞總數(shù)、中性粒細(xì)胞及嗜酸性細(xì)胞比例均明顯高于其余四組;肥胖哮喘小鼠血清、肺組織中TGF-β的水平、氣管壁厚度(WAt/Pbm)、平滑肌厚度(WAm/Pbm)均高于對(duì)照組、肥胖組、布地奈德治療組、吡非尼酮干預(yù)組。肥胖組BALF白細(xì)胞總數(shù)、嗜酸性粒細(xì)胞比例均略高于對(duì)照組,差異無統(tǒng)計(jì)學(xué)意義(P0.05);吡非尼酮干預(yù)組及布地奈德治療組小鼠BALF的細(xì)胞總數(shù)、中性粒細(xì)胞比例和嗜酸性粒細(xì)胞比例較肥胖哮喘組均明顯減少(P0.05),吡非尼酮干預(yù)組BALF中嗜酸性粒細(xì)胞比例較布地奈德治療組減少(P0.05),但兩組中性粒細(xì)胞比例下降不明顯(P0.05);吡非尼酮干預(yù)組及布地奈德治療組WAt/Pbm、WAm/Pbm均較肥胖哮喘組明顯降低(P0.05),吡非尼酮干預(yù)組WAt/Pbm較布地奈德治療組降低(P0.05),WAm/Pbm兩組比較差異無統(tǒng)計(jì)學(xué)意義(P0.05);小鼠血清中及肺組織中TGF-β水平按照肥胖哮喘組、布地奈德治療組、吡非尼酮治療組、肥胖組、對(duì)照組依次遞減(P0.05),吡非尼酮干預(yù)組下降最為明顯(P0.05)。結(jié)論:TGF-β在肥胖哮喘小鼠氣道中高表達(dá),其高表達(dá)與氣道炎癥、氣道高分泌及氣道重塑有密切關(guān)系,吡非尼酮能有效抑制氣道炎癥,達(dá)到改善氣道炎癥及氣道重塑的作用。
[Abstract]:Aim: to investigate the effect of TGF- 尾 on airway remodeling in obese asthmatic mice and the effect of pifenidone. Methods: 75 healthy female C57BL/6J mice were randomly divided into three groups: control group A, obesity group B, obese asthma group C, budesonide treatment group D and pifenidone treatment group. Obesity was induced by high-fat diet in all the obese mice. The asthmatic model was established by intraperitoneal injection of ovalbumin and aerosol inhalation in mice in CfD E group, and the normal diet was used in all the mice in the control group. At the same time, saline was given to sensitize and excite. The mice in budesonide group were given budesonide suspension aerosol inhalation (0.5 mg / ml) for 30 min / time, pifenidone group was treated with pifenidone (300 mg / kg) drinking water, and the rest group was given normal drinking water. After 4 weeks of treatment, BALF was collected from mouse bronchoalveolar lavage fluid for cell count and classification. Airway inflammation, airway remodeling and airway mucus secretion were observed by PAS-Masson staining. The concentration of TGF- 尾 in serum was measured by ELISA method, and the expression of TGF- 尾 in right lung tissue was detected by Westernblot. The total area of trachea wall, airway smooth muscle area (Wam) and the circumference of basal membrane of the tube were measured by computer image analysis software. Results: the body weight of obese group was significantly higher than that of control group (P 0.05). In the course of sensitizing and arousing, the asthmatic mice in each group showed different degrees of acute asthma attack. At the end of the intervention, there was no death in all groups. The percentage of leukocytes, neutrophils and eosinophils in BALF of obese asthmatic mice was significantly higher than that of the other four groups, and the levels of TGF- 尾 in serum and lung tissue, thickness of trachea wall and thickness of smooth muscle were significantly higher in obese asthmatic mice than in control group. Obesity group, budesonide treatment group, pifenidone intervention group. The total number of BALF leukocytes and the percentage of eosinophil in obese group were slightly higher than those in control group, the difference was not statistically significant (P 0.05), the total number of BALF cells in pifenidone intervention group and budesonide treatment group was higher than that in control group. The percentage of neutrophils and eosinophil in BALF in the pifenidone intervention group was lower than that in the budesonide treatment group, but the percentage of neutrophils in both groups was not clear, but the percentage of eosinophilic granulocytes in the treatment group was significantly lower than that in the obese asthmatic group. Compared with obese asthma group, the WAt/Pbm of pifenidone intervention group and budesonide treatment group was significantly lower than that of obese asthmatic group, and the WAt/Pbm of pifenidone intervention group was lower than that of budesonide treatment group. There was no significant difference between the two groups. The levels of TGF- 尾 in the tissue were determined according to the obesity asthma group. Budesonide treatment group, pifenidone treatment group, obesity group, the control group decreased in turn (P 0.05), pifenidone intervention group decreased the most significantly (P 0.05). Conclusion the high expression of TGF- 尾 in the airway of obese asthmatic mice is closely related to airway inflammation, airway hypersecretion and airway remodeling. Pifenidone can effectively inhibit airway inflammation and improve airway remodeling.
【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R562.25

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相關(guān)期刊論文 前4條

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