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地塞米松联合缬沙坦对小鼠慢性阻塞性肺疾病的保护作用及其机制

[Protective effects of dexamethasone combined with valsartan on chronic obstructive pulmonary disease in mice and its mechanism].

作者信息

Li Yong-Rong, Xie Hai-Bin, Li Hong, Sun Jie

机构信息

Department of Lung Disease, Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Lanzhou 730020.

Department of Geriatrics, Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Lanzhou 730020.

出版信息

Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2022 Mar;38(2):149-153. doi: 10.12047/j.cjap.6202.2022.019.

DOI:10.12047/j.cjap.6202.2022.019
PMID:36031573
Abstract

To investigate the possible protective effects of combined dexamethasone and valsartan against cigarette induced chronic obstructive pulmonary disease (COPD) in mice. Forty C57BL/6 mice were randomly divided into control group, COPD group, dexamethasone treated group, valsartan treated group and dexamethasone + valsartan combined treatment group, with 8 mice in each group. Mice in COPD group were exposed to cigarette for 8 weeks. On the basis of cigarette exposure, mice in dexamethasone treated group were intraperitoneally injected with dexamethasone (2 mg / kg) before cigarette exposure for 5-8 weeks. Mice in valsartan treated group were intraperitoneally injected with valsartan (30 mg/kg) before cigarette exposure for 1-8 weeks. Dexamethasone (2 mg/kg) and valsartan (30 mg/kg) were injected intraperitoneally into mice in the dexamethasone + valsartan combined treatment group. After 8 weeks, the lung tissues and bronchoalveolar lavage fluid (BALF) of mice in each group were collected. The pathological score of lung tissue was evaluated. The activities of superoxide dismutase(SOD) and matrix metalloproteinase-9 (MMP-9), and the contents of malondialdehyde (MDA), intracellular adhesion molecule-1 (ICAM-1), C-reactive protein (CRP) and nitric oxide (NO) in BALF were determined. Compared with the control group, COPD mice had emphysema and alveolar congestion, the levels of MDA, ICAM-1, MMP-9, CRP and lymphocytes in BALF were increased, while the levels of SOD, macrophages and NO were decreased (all <0.05). Compared with COPD group, there was no significant improvement in emphysema and alveolar congestion, the levels of SOD and NO in BALF were increased, and the levels of MDA, lymphocytes and macrophages were decreased in dexamethasone or valsartan group (all <0.05). Compared with dexamethasone or valsartan group, the dexamethasone + valsartan combined treatment was more effective in preventing pulmonary emphysema and alveolar congestion caused by cigarette smoke. The levels of MDA, ICAM-1, MMP-9, CRP and lymphocyte in BALF were decreased, while the levels of SOD, macrophage and NO were increased (all <0.05). Compared with dexamethasone or valsartan, dexamethasone combined with valsartan has a more effective protective effect in COPD mice by inhibiting oxidative stress and inflammation.

摘要

探讨地塞米松与缬沙坦联合应用对香烟诱导的小鼠慢性阻塞性肺疾病(COPD)的可能保护作用。将40只C57BL/6小鼠随机分为对照组、COPD组、地塞米松治疗组、缬沙坦治疗组和地塞米松+缬沙坦联合治疗组,每组8只。COPD组小鼠暴露于香烟8周。在香烟暴露的基础上,地塞米松治疗组小鼠在香烟暴露前5 - 8周腹腔注射地塞米松(2mg/kg)。缬沙坦治疗组小鼠在香烟暴露前1 - 8周腹腔注射缬沙坦(30mg/kg)。地塞米松+缬沙坦联合治疗组小鼠腹腔注射地塞米松(2mg/kg)和缬沙坦(30mg/kg)。8周后,收集各组小鼠的肺组织和支气管肺泡灌洗液(BALF)。评估肺组织的病理评分。测定BALF中超氧化物歧化酶(SOD)和基质金属蛋白酶-9(MMP-9)的活性,以及丙二醛(MDA)、细胞间黏附分子-1(ICAM-1)、C反应蛋白(CRP)和一氧化氮(NO)的含量。与对照组相比,COPD小鼠出现肺气肿和肺泡充血,BALF中MDA、ICAM-1、MMP-9、CRP和淋巴细胞水平升高,而SOD、巨噬细胞和NO水平降低(均P<0.05)。与COPD组相比,地塞米松或缬沙坦组的肺气肿和肺泡充血无明显改善,BALF中SOD和NO水平升高,MDA、淋巴细胞和巨噬细胞水平降低(均P<0.05)。与地塞米松或缬沙坦组相比,地塞米松+缬沙坦联合治疗在预防香烟烟雾引起的肺气肿和肺泡充血方面更有效。BALF中MDA、ICAM-1、MMP-9和CRP以及淋巴细胞水平降低,而SOD、巨噬细胞和NO水平升高(均P<0.05)。与地塞米松或缬沙坦相比,地塞米松联合缬沙坦通过抑制氧化应激和炎症对COPD小鼠具有更有效的保护作用。

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