溴化结构域蛋白抑制剂JQ1对哮喘小鼠气道重塑作用机制研究

发布时间：2018-03-21 13:31

本文选题：JQ　切入点：哮喘　出处：《中国当代儿科杂志》2017年12期 　论文类型：期刊论文

【摘要】：目的探讨溴化结构域蛋白抑制剂JQ1对哮喘小鼠气道重塑治疗的分子学机制。方法将24只小鼠随机分成对照组、OVA诱导哮喘组(OVA组)、JQ1干预哮喘组(JQ1+OVA组)(n=8)。采用OVA致敏/激发制备哮喘小鼠模型,雾化激发前1h,JQ1+OVA组小鼠经腹腔注射JQ1溶液(50μg/g)。末次激发24h后留取支气管肺泡灌洗液(BALF)及肺组织,计算各组BALF中细胞总数及嗜酸性粒细胞百分比,肺组织行病理染色观察各组小鼠肺组织病理改变;采用RT-PCR及Westernblot法分别检测小鼠肺上皮间质转化(EMT)过程中钙黏蛋白(E-Cadherin)、波形蛋白(vimentin)m RNA及蛋白水平的表达变化。结果与对照组比较,OVA组小鼠气道炎性细胞明显浸润,气道壁增厚,黏液渗出增多;BALF中细胞总数增加,嗜酸性粒细胞百分比增多(P0.01)。与OVA组比较,JQ1+OVA组小鼠气道炎症反应明显减轻;BALF中细胞总数明显减少,嗜酸性粒细胞百分比降低(P0.01)。与对照组比较,OVA组小鼠肺组织气道上皮E-Cadherinm RNA及蛋白表达水平明显下调,vimentinm RNA及蛋白表达水平明显上调(P0.01);与OVA组比较,JQ1+OVA组E-Cadherinm RNA及蛋白表达水平升高,vimentinm RNA及蛋白表达水平下降(P0.01);JQ1+OVA组与对照组上述指标表达水平比较差异无统计学意义(P0.05)。结论 OVA哮喘小鼠存在EMT气道重塑;溴化结构域蛋白抑制剂JQ1可降低哮喘小鼠气道炎症,抑制EMT,减轻气道重塑,为哮喘治疗提供了一个潜在的新方向。
[Abstract]:Objective to investigate the molecular mechanism of brominated domain protein inhibitor (JQ1) in the treatment of airway remodeling in asthmatic mice. Methods 24 mice were randomly divided into control group (OVA-induced asthma group) and JQ1 intervention group (JQ1 OVA group). OVA was used to sensitize the mice. / induced asthma mouse model, The mice in JQ1 OVA group were injected intraperitoneally with 50 渭 g / g JQ1 solution 1 hour before atomization. The bronchoalveolar lavage fluid (BALF) and lung tissue were collected 24 hours after the last stimulation. The total number of cells in BALF and the percentage of eosinophils in each group were calculated. The pathological changes of lung tissue in each group were observed by pathological staining. The expression of E-Cadherin, vimentin, vimentin RNA and protein during the process of lung epithelial interstitial transformation in mice were detected by RT-PCR and Westernblot. Results compared with the control group, the airway inflammatory cells infiltrated obviously and the airway wall became thicker in the OVA group. Compared with the OVA group, the airway inflammatory response in the JQ1 OVA group was significantly reduced, and the total number of the cells in the BALF was significantly decreased compared with that in the OVA group, while the percentage of eosinophils in the BALF was increased and the percentage of eosinophilic granulocytes in the BALF was increased. The percentage of eosinophilic granulocytes decreased (P 0.01). Compared with the control group, the expression of E-Cadherinm RNA and protein in the lung epithelium of the OVA group significantly decreased the expression level of vimentinm RNA and protein, and the expression of E-Cadherinm RNA and protein in the JQ1 OVA group was significantly up-regulated than that in the OVA group, and the expression of E-Cadherinm RNA and protein in JQ1 OVA group was significantly higher than that in the OVA group. There was no significant difference in the expression level of RNA and protein between the P0.01JQ1 OVA group and the control group. Conclusion there is EMT remodeling in the airway of OVA asthmatic mice. Brominated domain protein inhibitor (JQ1) can reduce airway inflammation, inhibit EMTs and reduce airway remodeling in asthmatic mice.
【作者单位】：南昌大学医学院;江西省人民医院呼吸科;江西省人民医院中心实验室;江西省儿童医院中心实验室;
【基金】：江西省科技厅重大科研基金(20151BBB70267)
【分类号】：R-332;R562.25

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