实用医学杂志 ›› 2022, Vol. 38 ›› Issue (6): 731-737.doi: 10.3969/j.issn.1006⁃5725.2022.06.016

• 基础研究 • 上一篇    下一篇

地塞米松对哮喘模型小鼠肺组织活性氧及线粒体基因MTCO1的影响

颜鹏1 邓育琼2 黄杏兰2 黄彩凤2 赵晓庆2 刘升2 程喜平2 刘晓东1   

  1. 广州医科大学附属第一医院 1 广州呼吸健康研究院呼吸疾病国家重点实验室,国家呼吸系统疾病临床医 学研究中心,2 皮肤科(广州 510180)

  • 出版日期:2022-03-25 发布日期:2022-03-25
  • 通讯作者: 刘晓东 E⁃mail:liuxd1013@126.com;程喜平 E⁃mail:cxpsyggyx@126.com
  • 基金资助:
    国家自然科学基金(编号:81673983,82074172);广东省自然科学基金面上项目(编号:2019A1515011930);广州市科技计
    划项目(编号:201607010355);广东省钟南山医学基金会⁃广州呼吸健康研究院自主课题(编号:ZNSA⁃2020013)

Effects of dexamethasone on the reactive oxygen species and MT⁃CO1 in lung tissues of asthma mice

YAN Peng*,DENG Yuqiong,HUANG Xinglan,HUANG Caifeng,ZHAO Xiaoqing,LIU Sheng,CHENG Xiping,LIU Xiaodong.    

  1. The First Affiliated Hospital,Guangzhou Medical University,the State Key Laboratory of Respiratory Dis⁃ ease,Guangzhou 510180,China

  • Online:2022-03-25 Published:2022-03-25
  • Contact: LIU Xiaodong E⁃mail:liuxd1013@126.com;CHENG Xiping E⁃mail:cxpsyggyx@126.com

摘要:

目的 探讨地塞米松对哮喘模型小鼠肺组织活性氧、线粒体基因MTCO1的影响。方法 动物 实验采用 BALB/C 小鼠利用卵清蛋白诱导生成哮喘模型鼠,21 只小鼠分为地塞米松组、哮喘组、空白组;所 有实验小鼠检测丙二醛;使用 qPCR WB 检测肺组织 MTCO1。细胞分为地塞米松组、IL⁃5 组、空白组。荧 光检测线粒体活性氧、线粒体膜电位,使用 qPCR WB 检测线粒体 MTCO1。结果 哮喘组和地塞米松组 肺组织中丙二醛组较空白组增高(P < 0.05),地塞米松组较哮喘组进一步增高(P < 0.05);qPCR 示哮喘组 和地塞米松组肺组织中的 MTCO1 较空白组降低(P < 0.05);地塞米松组 MTCO1 较哮喘组降低(P < 0.05); WB 结果与 qPCR 具有相同的趋势。细胞中 IL⁃5 组及地塞米松组的 MTCO1 对比空白组均降低(P < 0.05), 地塞米松组较 IL5 组进一步降低,差异无统计学意义(P > 0.05);对比空白组,IL⁃5 干预组及地塞米松组的 线粒体活性氧均增高,地塞米松组线粒体活性氧较 IL⁃5 组有增高的趋势;IL⁃5 组、地塞米松组线粒体膜电 位较空白组均降低,对比地塞米松组线粒体膜电位较 IL⁃5 组,有降低的趋势。结论 地塞米松降低哮喘 肺组织中已异常下降的 MTCO1 表达并升高哮喘肺组织中已异常升高的活性氧,不利于哮喘的缓解。糖皮质激素通过线粒体途径调控作用可以增强氧化应激反应,可能是哮喘不定期发作的潜在危险因素,抗氧化可能缓解在糖皮质激素通过线粒体途径调控造成对哮喘的不利影响。

关键词:

哮喘, 地塞米松, 活性氧, 线粒体呼吸链基因, 氧化应激, 免疫炎症, 小鼠

Abstract:

Objective To investigate the effects of dexamethasone on the reactive oxygen species and MT⁃CO1 in lung tissues of asthma mice. Methods The asthma model was induced by egg albumin with BALB/C mice. A total of 21 BALB/C mice were randomly assigned into control group,asthma group and dexamethasone group. Biochemical kits were used to detect malondialdehyde in all the animals,and Western blot and qPCR to detect protein and mRNA expressions of MTCO1 in their lung tissues. The 16HBE cells were further divided control group,IL ⁃5 group and dexamethasone group. mitochondrial reactive oxygen species,across which mitochondrial membrane potential was detected by fluorescence and the protein and mRNA expressions of MT ⁃CO1 by Western blot and qPCR. Results The MDA in the lung tissues of the asthma group and thedexamethasone group was sig⁃ nificantly higher than that in the control group(P < 0.05),and the MDA in thedexamethasone group was higher than that in the asthma group. The mRNA expression of MT⁃CO1 in the asthma group and thedexamethasone group was significantly higher than that in the control group(P < 0.05). The mRNA expression of MT⁃CO1 in the dexa⁃ methasone group was significantly higher than that in the asthma group(P < 0.05)and the westernblot showedthe same scenarioas qPCR. The MT⁃CO1 mRNA expression in the 16HBE,dexamethasone group and IL⁃5 group was significant decreased than that in the control group,and the express in the dexamethasone groupwas even lower than that in the IL⁃5 group but without significant. The mitochondrial reactive oxygen species in the 16HBE:dexa⁃methasone group and IL⁃5 group were significant increased than those in the control group,and the species in the dexamethasone groupwere increased to a higher extent than in the IL⁃5 group. The mitochondrial membrane poten⁃ tial in 16HBE:dexamethasone group and IL ⁃ 5 group were more significantly decreased than that in the control group,andthe potential in the dexamethasone groupwas increased to a higher extent than that in the IL ⁃ 5 group. Conclusion Dexamethasone can reduce the expression of MT⁃CO1 and further increase the level of reactive oxy⁃ gen species in lung tissue of asthmamice. Our result suggest that glucocorticoid can boost oxidative stress through mitochondrion dysfunction,which would be risk factor for irregular relapse of asthma. Antioxidation might alleviate detrimental effects of asthma through mitochondrion dysfunction caused by glucocorticoids. 

Key words:

asthma, dexamethasone, reactiveoxygenspecies, mitochondrial respiratory chain gene, oxidative stress, immune inflammation, mice