【摘要】：[背景]近年來很多研究顯示肥胖可能導(dǎo)致和加重支氣管哮喘(簡(jiǎn)稱哮喘)且二者在一定程度上存在相互作用,而哮喘和肥胖的全球發(fā)病率均呈逐年升高趨勢(shì)。[目的]為了探討Th-17淋巴細(xì)胞Th17及相關(guān)因子在肥胖哮喘小鼠的改變及其與氣道炎癥和重構(gòu)的關(guān)系,探討PPAR γ激動(dòng)劑對(duì)肥胖哮喘小鼠的治療效果及其與Th-17及相關(guān)因子的關(guān)系[方法]60只雌性C57/6J小鼠隨機(jī)分為哮喘組(A組),肥胖哮喘組(B組),對(duì)照組(C組)和治療組(D組),每組15只。A組小鼠卵白蛋白腹腔注射與霧化吸入建立哮喘模式,B組小鼠卵白蛋白腹腔注射和高脂飲食誘導(dǎo)制作肥胖哮喘模型,C組小鼠生理鹽水腹腔注射和普通飲食,D組小鼠卵白蛋白腹腔注射和高脂飲食并以PPAR γ激動(dòng)劑霧化處理。將各組小鼠稱量體質(zhì)量,對(duì)支氣管肺泡灌洗液(BALF)計(jì)量白細(xì)胞總數(shù)并對(duì)其進(jìn)行分類,ELISA法測(cè)定BALF中IL-4、IL-6及肺組織勻漿中IL-17、 IL-23和8-異前列腺素2a (8-iso-PGF2a)水平,肺組織切片后對(duì)各組小鼠氣道的病理變化進(jìn)行比較,測(cè)定各組小鼠的氣管壁總面積(WAt)、平滑肌而積(WAm)、管腔基底膜周長(zhǎng)(Pbm), westernblot測(cè)定PPAR γ的表達(dá)。[結(jié)果]A組、B組和D組小鼠支氣管肺泡灌洗液中白細(xì)胞總數(shù)、嗜酸性粒細(xì)胞比例以及BALF中IL-4、 IL-6水平明顯高于C組(P0.05),上述指標(biāo)B組A組D組,(P0.05)。A組、B組小鼠肺組織勻漿的8-iso-PGF2a高于C組,同時(shí)B組A組,差異均有統(tǒng)計(jì)學(xué)意義(P0.05)。A組、B組和D組的氣道重建程度(WAt/Pbm和WAm/Pbm)均明顯高于對(duì)照組(P0.05),其中WAt/Pbm B組A組D組,。A組、B組、D組小鼠肺組織勻漿內(nèi)IL-17和IL-23水平較C組明顯升高,且B組A組D組,,差異有統(tǒng)計(jì)學(xué)意義(P0.05). Pearson相關(guān)分析表明,IL-17與BALF的IL-6以及肺勻漿8-iso-PGF2a存在相關(guān)性,r分別為：0.816和0.731,P0.01。westernblot檢查發(fā)現(xiàn)肺組織核蛋白中PPAR γ的表達(dá)治療組較肥胖哮喘組增加[結(jié)論]肥胖哮喘小鼠Th17細(xì)胞增加,參與了哮喘氣道炎癥、氣道重塑和氧化應(yīng)激過程,抑制Thl7偏移可望成為肥胖哮喘治療的有效措施。PPAR γ激動(dòng)劑——羅格列酮能明顯改善氣道的炎癥反應(yīng)、氣道重建以及血.管重建。
[Abstract]:[BACKGROUND] In recent years, many studies have shown that obesity may lead to and aggravate the bronchial asthma ("asthma") and both have a certain degree of interaction, while the global incidence of asthma and obesity is increasing year by year. [Objective] To study the changes of Th-17 lymphocytes Th17 and related factors in obese asthma mice and their relationship with airway inflammation and remodeling. The effect of PPAR agonist on the treatment of obese asthma mice and its relationship with Th-17 and related factors[method] 60 female C57/ 6J mice were randomly divided into the group of asthma (group A), the obese asthma group (group B), the control group (group C) and the treatment group (group D), each group of 15 mice. The model of asthma was established by intraperitoneal injection and inhalation of ovalbumin in group A, and the model of obesity was induced by intraperitoneal injection of ovalbumin in group B and high-fat diet. Group D mouse ovalbumin was injected intraperitoneally with high-fat diet and treated with PPAR agonist. The levels of IL-17, IL-23 and 8-isoprostaglandin 2a (8-iso-PGF2a) in BALF, IL-4, IL-6 and lung tissue homogenate were determined by means of ELISA. After the lung tissue sections were cut, the pathological changes of the airway of each group were compared, the total area of the tube wall (Wt), the smooth muscle and the volume of the smooth muscle (Wm), the circumference of the basement membrane (Pbm), and the expression of the PPAR were determined by Western blot. [Results] The levels of IL-4 and IL-6 in BALF of group A, group B and group D were significantly higher than that in group C (P0.05). The degree of airway remodeling in group A, group B and group D (WAt/ Pbm and WAm/ Pbm) in group A, group B and group D was significantly higher than that in control group (P0.05). The levels of IL-17 and IL-23 in group A, group B and D group were significantly higher than that in group C. Pearson correlation analysis showed that there was a correlation between IL-17 and IL-6 in BALF and 8-iso-PGF2a of lung homogenate, r = 0.816 and 0.731, P 0.01. In the process of airway remodeling and oxidative stress, the inhibition of Thl7 migration is expected to be an effective measure for the treatment of obesity. PPAR agonist _ rosiglitazone can improve airway inflammation, airway remodeling and blood. Tube reconstruction.
【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】：2013
【分類號(hào)】：R562.25

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