地塞米松联合缬沙坦对慢性阻塞性肺疾病小鼠保护作用及机制探讨*

doi:10.12047/j.cjap.6202.2022.019

中国应用生理学杂志 ›› 2022, Vol. 38 ›› Issue (2): 149-153.doi: 10.12047/j.cjap.6202.2022.019

地塞米松联合缬沙坦对慢性阻塞性肺疾病小鼠保护作用及机制探讨^*

李永荣¹, 谢海彬², 李红³, 孙杰^4△

1.甘肃中医药大学附属医院肺病科, 兰州 730020;
2.甘肃中医药大学附属医院老年病科, 兰州 730020;
3.深圳市罗湖区中医院呼吸科, 深圳 518001;
4.广州中医药大学第一附属医院心肺康复科, 广州 510405

收稿日期:2021-04-08 修回日期:2022-03-26 出版日期:2022-03-28 发布日期:2022-08-29
通讯作者: ^△Tel: 13893358576; E-mail: 13893358576@163.com
基金资助:
^*国家自然科学基金(81560743)

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

LI Yong-rong¹, XIE Hai-bin², LI Hong³, SUN Jie^4△

1. Department of Lung Disease, Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Lanzhou 730020;
2. Department of Geriatrics, Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Lanzhou 730020;
3. Department of Respiratory, Luohu District Hospital of Traditional Chinese Medicine, Shenzhen 518001;
4. Department of Cardiorespiratory Rehabilitation, the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou 510405, China

Received:2021-04-08 Revised:2022-03-26 Online:2022-03-28 Published:2022-08-29

摘要/Abstract

摘要： 目的: 评估地塞米松联合缬沙坦对香烟所致慢性阻塞性肺疾病(COPD)小鼠的保护作用。方法: 40只C57BL/6小鼠随机分为(n=8):对照组、COPD组、地塞米松组、缬沙坦组和地塞米松+缬沙坦联合处理组。COPD组小鼠持续8周进行香烟暴露;在香烟暴露基础上,地塞米松组小鼠在5~8周香烟暴露前腹腔注射地塞米松(2 mg/kg);缬沙坦组小鼠在1~8周香烟暴露前腹腔注射缬沙坦(30 mg/kg);地塞米松+缬沙坦联合处理组小鼠腹腔注射地塞米松(2 mg/kg)和缬沙坦(30 mg/kg)。8周后收集各组小鼠肺组织及支气管肺泡灌洗液(BALF),评估肺组织病理学评分及BALF中超氧化物歧化酶(SOD)和基质金属蛋白酶9(MMP-9)活性,以及丙二醛(MDA)、细胞内黏附分子1(ICAM-1)、C反应蛋白(CRP)和一氧化氮(NO)含量。结果: 与对照组相比,COPD组小鼠存在肺气肿和肺泡充血,BALF中MDA、ICAM-1、MMP-9、CRP和淋巴细胞升高,SOD、巨噬细胞和NO降低(P均＜0.05)。与COPD组相比,地塞米松或缬沙坦组小鼠肺气肿和肺泡充血无明显改善,BALF中SOD 和NO升高,MDA、淋巴细胞和巨噬细胞降低(P均＜0.05)。与地塞米松或缬沙坦组相比较,地塞米松+缬沙坦联合处理组能更有效预防香烟引起的肺气肿和肺泡充血,降低BALF中MDA、ICAM-1、MMP-9、CRP和淋巴细胞,升高SOD、巨噬细胞和NO(P均＜ 0.05)。结论: 地塞米松联合缬沙坦通过抑制氧化应激和炎症,可以更有效在COPD小鼠中发挥保护作用。

关键词: 地塞米松, 缬沙坦, 慢性阻塞性肺疾病, 小鼠

Abstract: Objective: To investigate the possible protective effects of combined dexamethasone and valsartan against cigarette induced chronic obstructive pulmonary disease (COPD) in mice. Methods: 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. Results: 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 P＜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 P＜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 P＜0.05). Conclusion: Compared with dexamethasone or valsartan, dexamethasone combined with valsartan has a more effective protective effect in COPD mice by inhibiting oxidative stress and inflammation.

Key words: dexamethasone, valsartan, chronic obstructive pulmonary disease, mice

中图分类号:

R563.3

李永荣, 谢海彬, 李红, 孙杰. 地塞米松联合缬沙坦对慢性阻塞性肺疾病小鼠保护作用及机制探讨^*[J]. 中国应用生理学杂志, 2022, 38(2): 149-153.

LI Yong-rong, XIE Hai-bin, LI Hong, SUN Jie. Protective effects of dexamethasone combined with valsartan on chronic obstructive pulmonary disease in mice and its mechanism[J]. CJAP, 2022, 38(2): 149-153.

参考文献

[1] 李艳君, 周红. 慢性阻塞性肺疾病患者在戒烟中获益的相关研究进展[J]. 国际呼吸杂志, 2019, 39(12): 952-955.
[2] Hox V, Lourijsen E, Jordens A, et al. Benefits and harm of systemic steroids for short- and long-term use in rhinitis and rhinosinusitis: an EAACI position paper[J]. Clin Transl Allergy, 2020, 10(1): 1-27.
[3] Tamimi A, Serdarevic D, Hanania NA. The effects of cigarette smoke on airway inflammation in asthma and COPD: Therapeutic implications[J]. Respir Med, 2012, 106(3): 319-328.
[4] Podowski M, Calvi C, Metzger S, et al. Angiotensin receptor blockade attenuates cigarette smoke-induced lung injury and rescues lung architecture in mice[J]. J Clin Invest, 2012, 122(1): 229-240.
[5] Chunhua M, Long H, Zhu W, et al. Betulin inhibited cigarette smoke-induced COPD in mice[J]. Biomed Pharmacother, 2017, 85: 679-686.
[6] Podowski M, Calvi C, Metzger S, et al. Angiotensin receptor blockade attenuates cigarette smoke-induced lung injury and rescues lung architecture in mice[J]. J Clin Invest, 2012, 122(1): 229-240.
[7] 徐英, 霍建民. 香烟烟雾暴露诱导气道炎症相关机制和治疗潜力的研究进展[J]. 国际呼吸杂志, 2015, 35(4): 309-312.
[8] Fischer B, Pavlisko E, Voynow J. Pathogenic triad in COPD: oxidative stress, protease-antiprotease imbalance, and inflammation[J]. Int J Chron Obstruct Pulmon Dis, 2011, 6: 413-421.
[9] Chen T, Jiang W, Zhang H, et al. Protective effect of trillin against ethanol-induced acute gastric lesions in an animal model[J]. RSC Adv, 2016, 6(24): 20081-20088.
[10] Abdel-Latif GA, Elwahab AHA, Hasan RA, et al. A novel protective role of sacubitril/valsartan in cyclophosphamide induced lung injury in rats: impact of miRNA-150-3p on NF-κB/MAPK signaling trajectories[J]. Scientific Reports, 2020, 10(1): 13045.
[11] Prado CM, Leick-Maldonado EA, Yano L, et al. Effects of nitric oxide synthases in chronic allergic airway inflammation and remodeling[J]. Am J Resp Cell Molr Biol, 2006, 35(4): 457-465.
[12] Carr A, Frei B. The role of natural antioxidants in preserving the biological activity of endothelium-derived nitric oxide[J]. Free Radical Bio Med, 2000, 28(12): 1806-1814.
[13] 陈娟, 崔节达, 郭晓桐, 等. 慢性阻塞性肺疾病小气道NOX4、TGF-β的表达与气道重塑的关系[J]. 中国应用生理学杂志, 2017, 33(6): 481-487.
[14] Esa SA, Rawy AM, El-Behissy MM, et al. Study of the level of sputum matrix metalloproteinase-9(MMP-9) and tissue inhibitor metalloproteinase-1(TIMP-1) in COPD patients[J]. Egypt J Chest Dis Tuber, 2014, 63(4): 861-867.
[15] 白林林, 王志华, 宁学聪, 等. IL-17A对慢性阻塞性肺疾病的干预作用及其机制[J]. 中国应用生理学杂志, 2021, 37(6): 584-588.
[16] Yu N, Sun YT, Su XM, et al. Treatment witheucalyptol mitigates cigarette smoke-induced lung injury through suppressing ICAM-1 gene expression[J]. Biosci Rep, 2018, 38(4): BSR20171636.
[17] Liu L, Qiu HB, Yang Y, et al. Losartan, an antagonist of AT1 receptor for angiotensin II, attenuates lipopolysaccharide-induced acute lung injury in rat[J]. Arch Biochem Biophys, 2009, 481(1): 131-136.

地塞米松联合缬沙坦对慢性阻塞性肺疾病小鼠保护作用及机制探讨^*

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

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