引用本文:[点击复制]
[点击复制]
【打印本页】 【在线阅读全文】【下载PDF全文】 查看/发表评论下载PDF阅读器关闭

←前一篇|后一篇→

过刊浏览    高级检索

本文已被:浏览 276次   下载 47 本文二维码信息
码上扫一扫!
阿奇霉素对慢阻肺大鼠肺脏病理损伤、氧化应激及TLR4/NF -B信号通路的调节作用
赵朝华,廖和和,王甲林,李寒春,任明智,黄慧云,吴树强
0
(西安医学院基础医学部解剖教研室;陕西省核工业二一五医院肿瘤医疗中心;西安医学院第一附属医院肿瘤胸外科,西安大兴医院肿瘤胸外科)
摘要:
目的 探讨阿奇霉素(Azi)对慢性阻塞性肺疾病(COPD)模型大鼠肺脏病理损伤、氧化应激的影响及其机制。方法 选择6~8周龄雄性SD大鼠60只,随机分为对照组(Control组)、模型组(COPD组)和治疗组1(COPD+Azi25 mg)、治疗组2(COPD+Azi 50 mg)、治疗组3(COPD+Azi 100 mg)5组。通过烟熏联合气管内滴入脂多糖的方法诱导建立大鼠COPD模型。治疗组于烟熏前30 min给予对应浓度的阿奇霉素灌胃,对照组和模型组给予等量的生理盐水,1次/d,连续4周。测定右肺湿重/干重比值(W/D);HE和MASSON染色检测肺组织病理形态及纤维化情况;Western blot检测裂解形式的半胱天冬酶3(Caspase-3)、基质金属蛋白酶9(MMP9)的蛋白表达;RT-PCR和Western blot检测Toll样受体4(TLR4)、核因子κB(NFκB)p65和NF-B抑制蛋白(IkBα)的mRNA及蛋白表水平;ELISA法检测肿瘤坏死因子α(TNFα)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSHPx)和丙二醛(MDA)含量。 结果 与模型组相比,阿奇霉素治疗能降低W/D比值(P<0.05);减轻肺组织充血、水肿、炎性细胞浸润和胶原沉积;下调Caspase3、MMP-9蛋白表达(P<0.05);降低TNF、IL-1β和IL-6含量(P<0.05);增加SOD和GSHPx活性,降低MDA表达(P<0.05);同时抑制TLR4、NF-B p65和IκBα的磷酸化水平(P<0.05)。 结论 阿奇霉素能改善慢阻肺模型大鼠肺脏组织形态和纤维化,并抑制其氧化应激,这与抑制TLR4/NF-B信号通路激活有关。
关键词:  慢性阻塞性肺疾病  阿奇霉素  纤维化  TLR4/NF-B信号通路
DOI:
基金项目:陕西省自然科学专项(13JK0793);陕西省自然科学基础研究计划 (2018JM7065);陕西省教育厅科研计划项目 (16JK1645)
Regulation of azithromycin on lung pathological injury, oxidative stress and TLR4/NF-kB signaling pathway in COPD rats
ZHAO Zhaohua,LIAO Hehe,WANG Jialin,LI Hanchun,REN Mingzhi,HUANG Huiyun,WU Shuqiang
(Anatomy Teaching and Research Office,School of Basic Medical Sciences, Xi′an Medical University;Cancer Medical Center, The Nuclear Industry 215 Hospital;Tumor Thoracic Surgery, The First Affiliated Hospital of Xi′an Medical University,Tumor Thoracic Surgery, Xi′an Daxing Hospital)
Abstract:
Objective To investigate the effects and mechanism of Azithromycin (Azi) on lung pathological injury and oxidative stress in rats with chronic obstructive pulmonary disease (COPD). Methods Rats were randomly divided into control group, model group (COPD group) and treatment group 1(COPD+Azi(25 mg)), treatment group 2(COPD+Azi(50 mg)) and treatment group 3(COPD+Azi(100 mg)). The COPD rat model was induced by smoking combined with intratracheal instillation of lipopolysaccharide. The treatment groups were given Azi by gavage at 30 minutes before smoking. The control group and treatment groups were given the same amount of saline once a day for 4 weeks. The wet/dry weight ratio (W/D) of right lung was measured. The pathological morphology and fibrosis of lung tissue were detected by HE and MASSON staining. The protein expression of Caspase3 and MMP9 were detected by Western blot. The mRNA and protein expression of Tolllike receptor 4 (TLR4), nuclear factork B (NFkB) p65 and NF-kB inhibitor protein (IkBα) were detected by RTPCR and Western blot. The levels of tumor necrosis factorα(TNF), interleukin-1β (IL-1β), interleukin6 (IL-6), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were detected by the kit. Results Compared with model group, Azithromycin could reduce W/D ratio, pulmonary congestion, edema, inflammatory cell infiltration and collagen deposition, downregulate the protein expression of Caspase-3 and MMP-9 (P<0.05), inhibit the content of TNFα, IL-1β and IL-6 (P<0.05), increase SOD and GSHPx activity and decrease MDA content (P<0.05). At the same time, Azithromycin could inhibit the phosphorylation level of TLR4, NF-kB p65 and IkBα (P<0.05). Conclusion Azithromycin can improve the morphology and fibrosis of lung tissue and inhibit oxidative stress in COPD rats, which is related to the inhibition of activation of TLR4/NFkappa B signaling pathway.
Key words:  Chronic obstructive pulmonary disease  Azithromycin  Fibrosis  Toll-like receptor 4  Nuclear factor-kB

用微信扫一扫

用微信扫一扫