中国当代儿科杂志2017，Vol.19Issue(12)：1278-1284,7.DOI:10.7499/j.issn.1008-8830.2017.12.011
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
Mechanism of action of BET bromodomain inhibitor JQ1 in treating airway remodeling in asthmatic mice
摘要
Abstract
Objective To investigate the molecular mechanism of action of BET bromodomain inhibitor JQ1 in treating airway remodeling in asthmatic mice. Methods A total of 24 mice were randomly divided into control group, ovalbumin (OVA)-induced asthma group (OVA group), and JQ1 intervention group (JQ1+OVA group), with 8 mice in each group. OVA sensitization/challenge was performed to establish a mouse model of asthma. At 1 hour before challenge, the mice in the JQ1+OVA group were given intraperitoneal injection of JQ1 solution (50 μg/g). Bronchoalveolar lavage fluid (BALF) and lung tissue samples were collected at 24 hours after the last challenge, and the total number of cells and percentage of eosinophils in BALF were calculated. Pathological staining was performed to observe histopathological changes in lung tissue. RT-PCR and Western blot were used to measure the mRNA and protein expression of E-cadherin and vimentin during epithelial-mesenchymal transition (EMT). Results Compared with the control group, the OVA group had marked infiltration of inflammatory cells in the airway, thickening of the airway wall, increased secretion of mucus, and increases in the total number of cells and percentage of eosinophils in BALF (P<0.01). Compared with the OVA group, the JQ1+OVA group had significantly alleviated airway inflammatory response andsignificant reductions in the total number of cells and percentage of eosinophils in BALF (P<0.01). Compared with the control group, the OVA group had significant reductions in the mRNA and protein expression of E-cadherin and significant increases in the mRNA and protein expression of vimentin (P<0.01); compared with the OVA group, the JQ1+OVA group had significant increases in the mRNA and protein expression of E-cadherin and significant reductions in the mRNA and protein expression of vimentin (P<0.01); there were no significant differences in these indices between the JQ1+OVA group and the control group (P>0.05). Conclusions Mice with OVA-induced asthma have airway remodeling during EMT. BET bromodomain inhibitor JQ1 can reduce airway inflammation, inhibit EMT, and alleviate airway remodeling, which provides a new direction for the treatment of asthma.关键词
JQ1/哮喘/上皮间质转化/气道重塑/小鼠Key words
JQ1/Asthma/Epithelial-mesenchymal transition/Airway remodeling/Mice引用本文复制引用
朱晓华,李秋根,汪俊,胡国柱,刘志强,胡清华,吴刚..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[J].中国当代儿科杂志,2017,19(12):1278-1284,7.基金项目
江西省科技厅重大科研基金(20151BBB70267). （20151BBB70267）
