TH17在肥胖哮喘小鼠气道炎症中的作用及其与氧化应激的关系

发布时间：2019-03-06 15:38

【摘要】：[背景]近年来很多研究显示肥胖可能导致和加重支气管哮喘(简称哮喘)且二者在一定程度上存在相互作用,而哮喘和肥胖的全球发病率均呈逐年升高趋势。[目的]为了探讨Th-17淋巴细胞Th17及相关因子在肥胖哮喘小鼠的改变及其与气道炎症和重构的关系,探讨PPAR γ激动剂对肥胖哮喘小鼠的治疗效果及其与Th-17及相关因子的关系[方法]60只雌性C57/6J小鼠随机分为哮喘组(A组),肥胖哮喘组(B组),对照组(C组)和治疗组(D组),每组15只。A组小鼠卵白蛋白腹腔注射与雾化吸入建立哮喘模式,B组小鼠卵白蛋白腹腔注射和高脂饮食诱导制作肥胖哮喘模型,C组小鼠生理盐水腹腔注射和普通饮食,D组小鼠卵白蛋白腹腔注射和高脂饮食并以PPAR γ激动剂雾化处理。将各组小鼠称量体质量,对支气管肺泡灌洗液(BALF)计量白细胞总数并对其进行分类,ELISA法测定BALF中IL-4、IL-6及肺组织匀浆中IL-17、 IL-23和8-异前列腺素2a (8-iso-PGF2a)水平,肺组织切片后对各组小鼠气道的病理变化进行比较,测定各组小鼠的气管壁总面积(WAt)、平滑肌而积(WAm)、管腔基底膜周长(Pbm), westernblot测定PPAR γ的表达。[结果]A组、B组和D组小鼠支气管肺泡灌洗液中白细胞总数、嗜酸性粒细胞比例以及BALF中IL-4、 IL-6水平明显高于C组(P0.05),上述指标B组A组D组,(P0.05)。A组、B组小鼠肺组织匀浆的8-iso-PGF2a高于C组,同时B组A组,差异均有统计学意义(P0.05)。A组、B组和D组的气道重建程度(WAt/Pbm和WAm/Pbm)均明显高于对照组(P0.05),其中WAt/Pbm B组A组D组,。A组、B组、D组小鼠肺组织匀浆内IL-17和IL-23水平较C组明显升高,且B组A组D组,,差异有统计学意义(P0.05). Pearson相关分析表明,IL-17与BALF的IL-6以及肺匀浆8-iso-PGF2a存在相关性,r分别为：0.816和0.731,P0.01。westernblot检查发现肺组织核蛋白中PPAR γ的表达治疗组较肥胖哮喘组增加[结论]肥胖哮喘小鼠Th17细胞增加,参与了哮喘气道炎症、气道重塑和氧化应激过程,抑制Thl7偏移可望成为肥胖哮喘治疗的有效措施。PPAR γ激动剂——罗格列酮能明显改善气道的炎症反应、气道重建以及血.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.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R562.25

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