克拉霉素对激素反应性通路中组蛋白去乙酰化酶2及糖皮质激素受体的影响

发布时间：2018-10-15 18:42

【摘要】：目的观察克拉霉素对激素反应性通路中组蛋白去乙酰化酶2(HDAC2)及糖皮质激素受体(GR)的影响,探讨克拉霉素对烟雾暴露哮喘小鼠可能的治疗作用。方法选择BALB/c小鼠作为研究对象,通过卵蛋白致敏激发建立哮喘模型组(OVA组)、烟雾暴露哮喘组(SEA组)以及哮喘接触烟雾暴露后通过克拉霉素治疗组(CAM组),同时设立对照组平行比较。采用组织病理学检测各组小鼠肺组织炎症情况,并通过PCR检测肺组织中HDAC2mRNA的表达情况和Western blot检测肺组织中HDAC2和GR蛋白的表达。结果组织病理学观察OVA组和SEA组均存在肺组织气道炎症,其中SEA组纤毛被严重破坏,而CAM组炎症细胞浸润减弱。与CAM组相比,SEA组小鼠支气管肺泡灌洗液中IL-4和IL-8水平均显著提高(104.36±14.39 vs.65.49±10.82、681.35±66.18 vs.321.49±90.37,P=0.031、0.017)。CAM组HDAC2mRNA表达显著高于SEA组(0.062±0.013 vs.0.031±0.015,P=0.032)。Western blot检测结果显示,与CAM组相比,SEA组HDAC2蛋白(0.23±0.017 vs.0.49±0.022,P=0.033)和GR蛋白(0.19±0.014 vs.0.64±0.023,P=0.011)表达均显著降低。结论克拉霉素能抑制烟雾暴露的哮喘小鼠气道炎症反应,作用机制可能通过与GR相结合,影响下游HDAC2基因表达有关。
[Abstract]:Objective to observe the effects of clarithromycin on histone deacetylase 2 (HDAC2) and glucocorticoid receptor (GR) in hormone responsive pathway and to explore the possible therapeutic effects of clarithromycin on smog exposed asthma mice. Methods BALB/c mice were selected as study objects. Asthma model group (OVA group), asthmatic group (SEA group) exposed to smoke and Clarithromycin treated group (CAM group) after exposure to smoke were established by ovalbumin sensitization. The lung inflammation was detected by histopathology, the expression of HDAC2mRNA and the expression of HDAC2 and GR protein in lung tissue were detected by PCR and Western blot respectively. Results histopathological observation showed that there was airway inflammation in both OVA and SEA groups, in which the ciliates in SEA group were severely damaged, but inflammatory cell infiltration was weakened in CAM group. 涓嶤AM缁勭浉姣，

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