[1]刘雪君,佘晖,郑玲容,等.BRD4抑制剂JQ1对慢性阻塞性肺疾病模型小鼠肺功能的影响[J].福建医药杂志,2022,44(01):107-111.
　LIU Xuejun,SHE Hui,ZHENG Lingrong,et al.Effect of BRD4 inhibitor JQ1 on lung function in mice with chronic obstructive pulmonary disease[J].FUJIAN MEDICAL JOURNAL,2022,44(01):107-111.
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BRD4抑制剂JQ1对慢性阻塞性肺疾病模型小鼠肺功能的影响()
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《福建医药杂志》[ISSN:1002-2600/CN:35-1071/R]

卷:
44
期数:
2022年01期
页码:
107-111
栏目:
基础研究
出版日期:
2022-02-15

文章信息/Info

Title:
Effect of BRD4 inhibitor JQ1 on lung function in mice with chronic obstructive pulmonary disease
文章编号:
1002-2600(2022)01-0107-05
作者:
刘雪君; 佘晖1; 郑玲容; 王玲琼
厦门大学附属福州第二医院呼吸与危重症医学科(福州350007)
Author(s):
LIU Xuejun;  SHE Hui;  ZHENG Lingrong;  WANG Lingqiong
Department of Res piratory and Critical Care Medicine, the Affliated Municipal Second Hospital of Xiamen University, Fuzhou, Fujian 350007, China
关键词:
慢性阻塞性肺疾病; 肺功能;  BRD4;  JQ1; 气道重塑
Keywords:
COPD;  lung function;  BRD4;  JQl;  airway remodeling
分类号:
R563
文献标志码:
A
摘要:
目的 探讨溴结构域蛋白4抑制剂(JQ1)对慢性阻塞性肺疾病(COPD)小鼠肺功能的影响及其机制。方法 15只小鼠随机分成对照组、COPD模型组、JQ1治疗组，每组5只。采用24周慢性烟雾暴露联合脂多糖制备COPD小鼠模型，JQ1治疗组小鼠经5周腹腔注射JQ1溶液。治疗结束后检测各组小鼠第0.1秒用力呼气量与用力肺活量之比(FEV0.1/FVC)、最大呼气中期流速(MMF)、呼气峰流速(PEF)、呼气气道阻力(Re)、肺动态顺应性(Cdyn)。后留取小鼠眼球血及肺组织，对比各组小鼠炎症因子(IL-6、IL-8、TNF-α)及肺组织平均内衬间隔(MLI)、平均肺泡密度(MAN)、气道周围胶原面积占比和波形蛋白(vimentin VIM)等气道重塑指标情况。结果 与对照组 比较，COPD模型组的FEV0.1/FVC、PEF、MMF和Cdyn均显著降低，Re升高;与COPD模型组比较，JQ1治疗组的FEV0.1/FVC、PEF、MMF和Cdyn升高，Re降低。JQ1治疗组较COPD模型组小鼠血清及肺组织中的IL-6、IL-8、TNF-α降低;肺组织MLI减少、MAN增加，气道周围胶原蛋白沉积减少，VIM mRNA及蛋白表达水平降低。差异均有统计学意义(P<0.05)。 结论 BRD4抑制剂JQ1可能通过改善气道炎症及气道重塑来提高COPD模型组小鼠的肺功能。
Abstract:
Objective To explore the effect of bromodomain protein 4 (BRD4) inhibitor JQ1 on lung function in mice with chronic obstructive pulmonary disease (COPD) and its mechanism. Methods A total of 15 mice were randomly divided into control group, COPD group, and JQ1 intervention group, with 5 mice in each group. After 24 weeks of chronic CS/LPS exposure and 5 weeks of JQ1 treatment, the mice were anesthetized, and the lung function were determined including the changes of FEV0.1/FVC, maximal midexpiratory flow (MMF), peek expiration flow (PEF), resistance of expiration (Re), and respiratory dynamic compliance (Cdyn). Then eyeball blood and lung tissue samples were collected to determine the levels of IL-6,IL-8,and TNF-α,and the airway remodeling indexes, such as the mean alveolar number (MAN)，mean linear intercept (MLI)，the ratio of collagen area around airways, and the mRNA and protein expression of vimentin (VIM). Results In the COPD group, the FEV0.1/FVC, PEF, MMF, and Cdyn were significantly lower than those in the control group, while the Re was higher (P<0.05). Compared with the COPD group, JQ1 treatment could significantly alleviate the FEV0.1/FVC,PEF,MMF,and Cdyn, meanwhile decrease the Re (P<0.05). Contrast to the COPD group, the levels of IL-6,IL-8,and TNF-α in serum and lung tissue were significantly decreased in the JQ1 intervention group, as well as the levels of the mRNA and protein expression of VIM (P<0.05). The MLI and the ratio of collagen area around airways were significantly lower (P<0.05)， but the MAN was significantly higher (P<0.05) in the JQ1 intervention group. Conclusion The BRD4 inhibitor JQ1 may protect lung function of the mice with COPD via abrogating chronic CS/LPS induced airway inflammation and remodeling.

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备注/Memo

备注/Memo:
基金项目:福建省自然科学基金资助项目(2019J01542); 福建省科技计划项目(引导性项目，2019D005); 福州市科技计划项目(2018-S-101-1)
通信作者，Email:shui_317@163.com
更新日期/Last Update: 2022-02-15