本文選題：JQ　切入點(diǎn)：哮喘　出處：《中國(guó)當(dāng)代兒科雜志》2017年12期 　論文類(lèi)型：期刊論文

【摘要】：目的探討溴化結(jié)構(gòu)域蛋白抑制劑JQ1對(duì)哮喘小鼠氣道重塑治療的分子學(xué)機(jī)制。方法將24只小鼠隨機(jī)分成對(duì)照組、OVA誘導(dǎo)哮喘組(OVA組)、JQ1干預(yù)哮喘組(JQ1+OVA組)(n=8)。采用OVA致敏/激發(fā)制備哮喘小鼠模型,霧化激發(fā)前1h,JQ1+OVA組小鼠經(jīng)腹腔注射JQ1溶液(50μg/g)。末次激發(fā)24h后留取支氣管肺泡灌洗液(BALF)及肺組織,計(jì)算各組BALF中細(xì)胞總數(shù)及嗜酸性粒細(xì)胞百分比,肺組織行病理染色觀察各組小鼠肺組織病理改變;采用RT-PCR及Westernblot法分別檢測(cè)小鼠肺上皮間質(zhì)轉(zhuǎn)化(EMT)過(guò)程中鈣黏蛋白(E-Cadherin)、波形蛋白(vimentin)m RNA及蛋白水平的表達(dá)變化。結(jié)果與對(duì)照組比較,OVA組小鼠氣道炎性細(xì)胞明顯浸潤(rùn),氣道壁增厚,黏液滲出增多;BALF中細(xì)胞總數(shù)增加,嗜酸性粒細(xì)胞百分比增多(P0.01)。與OVA組比較,JQ1+OVA組小鼠氣道炎癥反應(yīng)明顯減輕;BALF中細(xì)胞總數(shù)明顯減少,嗜酸性粒細(xì)胞百分比降低(P0.01)。與對(duì)照組比較,OVA組小鼠肺組織氣道上皮E-Cadherinm RNA及蛋白表達(dá)水平明顯下調(diào),vimentinm RNA及蛋白表達(dá)水平明顯上調(diào)(P0.01);與OVA組比較,JQ1+OVA組E-Cadherinm RNA及蛋白表達(dá)水平升高,vimentinm RNA及蛋白表達(dá)水平下降(P0.01);JQ1+OVA組與對(duì)照組上述指標(biāo)表達(dá)水平比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論 OVA哮喘小鼠存在EMT氣道重塑;溴化結(jié)構(gòu)域蛋白抑制劑JQ1可降低哮喘小鼠氣道炎癥,抑制EMT,減輕氣道重塑,為哮喘治療提供了一個(gè)潛在的新方向。
[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.
【作者單位】： 南昌大學(xué)醫(yī)學(xué)院;江西省人民醫(yī)院呼吸科;江西省人民醫(yī)院中心實(shí)驗(yàn)室;江西省兒童醫(yī)院中心實(shí)驗(yàn)室;
【基金】：江西省科技廳重大科研基金(20151BBB70267)
【分類(lèi)號(hào)】：R-332;R562.25

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