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[1]劉雪君,佘暉,鄭玲容,等.BRD4抑制劑JQ1對慢性阻塞性肺疾病模型小鼠肺功能的影響[J].福建醫(yī)藥雜志,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抑制劑JQ1對慢性阻塞性肺疾病模型小鼠肺功能的影響()
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《福建醫(yī)藥雜志》[ISSN:1002-2600/CN:35-1071/R]

卷:
44
期數(shù):
2022年01期
頁碼:
107-111
欄目:
基礎(chǔ)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
文章編號(hào):
1002-2600(2022)01-0107-05
作者:
劉雪君; 佘暉1; 鄭玲容; 王玲瓊
廈門大學(xué)附屬福州第二醫(yī)院呼吸與危重癥醫(yī)學(xué)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
關(guān)鍵詞:
慢性阻塞性肺疾病; 肺功能;  BRD4;  JQ1; 氣道重塑
Keywords:
COPD;  lung function;  BRD4;  JQl;  airway remodeling
分類號(hào):
R563
文獻(xiàn)標(biāo)志碼:
A
摘要:
目的 探討溴結(jié)構(gòu)域蛋白4抑制劑(JQ1)對慢性阻塞性肺疾病(COPD)小鼠肺功能的影響及其機(jī)制。方法 15只小鼠隨機(jī)分成對照組、COPD模型組、JQ1治療組，每組5只。采用24周慢性煙霧暴露聯(lián)合脂多糖制備COPD小鼠模型，JQ1治療組小鼠經(jīng)5周腹腔注射JQ1溶液。治療結(jié)束后檢測各組小鼠第0.1秒用力呼氣量與用力肺活量之比(FEV0.1/FVC)、最大呼氣中期流速(MMF)、呼氣峰流速(PEF)、呼氣氣道阻力(Re)、肺動(dòng)態(tài)順應(yīng)性(Cdyn)。后留取小鼠眼球血及肺組織，對比各組小鼠炎癥因子(IL-6、IL-8、TNF-α)及肺組織平均內(nèi)襯間隔(MLI)、平均肺泡密度(MAN)、氣道周圍膠原面積占比和波形蛋白(vimentin VIM)等氣道重塑指標(biāo)情況。結(jié)果 與對照組 比較，COPD模型組的FEV0.1/FVC、PEF、MMF和Cdyn均顯著降低，Re升高;與COPD模型組比較，JQ1治療組的FEV0.1/FVC、PEF、MMF和Cdyn升高，Re降低。JQ1治療組較COPD模型組小鼠血清及肺組織中的IL-6、IL-8、TNF-α降低;肺組織MLI減少、MAN增加，氣道周圍膠原蛋白沉積減少，VIM mRNA及蛋白表達(dá)水平降低。差異均有統(tǒng)計(jì)學(xué)意義(P<0.05)。 結(jié)論 BRD4抑制劑JQ1可能通過改善氣道炎癥及氣道重塑來提高COPD模型組小鼠的肺功能。
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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備注/Memo

備注/Memo:
基金項(xiàng)目:福建省自然科學(xué)基金資助項(xiàng)目(2019J01542); 福建省科技計(jì)劃項(xiàng)目(引導(dǎo)性項(xiàng)目，2019D005); 福州市科技計(jì)劃項(xiàng)目(2018-S-101-1)
通信作者，Email:[email protected]
更新日期/Last Update: 2022-02-15