贝母素甲改善脂多糖联合烟雾诱导小鼠慢性阻塞性肺疾病的机制

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中文摘要：目的探讨贝母素甲(PME)对慢性阻塞性肺疾病(COPD)小鼠的作用和相关机制。方法将 80 只小鼠随机分为 4 组(每组 20 只):对照组、PME组、COPD组和治疗组。使用脂多糖联合烟雾诱导小鼠COPD动物模型。通过组织病理学、超微结构、小鼠肺组织湿/干重比值分析 PME 对 COPD 模型鼠结构的影响;ELISA和Western blotting分析PME对肺组织中炎症因子肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6 和IL-1β表达的影响;二氢乙锭(DHE)染色和 Western blotting分析 PME对肺组织中氧化应激反应的影响;Western blotting分析PME对核因子κB(NF-κB)通路以及核因子 2 相关因子 2(Nrf2)通路相关蛋白表达的影响。结果与COPD组相比，PME治疗可明显减轻小鼠肺组织的损伤和减少炎症细胞数量，降低肺组织湿/干重比。与对照组相比，COPD组小鼠的肺泡灌洗液中TNF-α、IL-6 及IL-1β水平明显增加，经PME治疗后小鼠肺泡灌洗液中TNF-α、IL-6及IL-1β水平明显降低。另外，与对照组相比，COPD组小鼠肺组织中TNF-α和IL-1β水平显著升高，经PME治疗后小鼠肺组织中TNF-α和IL-1β蛋白水平明显下降。免疫组织化学和Western blotting实验显示，与对照组相比，COPD组SOD2 水平明显降低，而PME治疗后能够提高超氧化物歧化酶(SOD)蛋白水平。对肺组织丙二醛(MDA)含量分析发现，与 COPD 组比较，PME 治疗后明显抑制 COPD 小鼠肺组织中 MDA 的产生。Western blotting结果显示，PME治疗后能够阻止肺组织中的NF-κB抑制蛋白(IκBα)磷酸化以及NF-κB p65 向细胞核转移，PME处理后的小鼠肺组织中Nrf2 及其主要下游靶点血红素加氧酶 1(HO-1)的表达明显升高。结论 PME能够抑制COPD小鼠体内的炎症和氧化应激反应，改善脂多糖联合烟雾诱导肺组织损伤，其机制可能与激活Nrf2 通路和抑制NF-κB通路相关。

外文标题：Mechanism of peimine improving chronic obstructive pulmonary disease induced by lipopolysaccharide combined with cigarette smoke in mice

外文摘要：Objective To investigate the effects and mechanisms of peimine(PME)on chronic obstructive pulmonary disease(COPD)in mice.Methods The mice were randomly divided into 4 groups(20 mice in each group),control group,PME group,chronic obstructive pulmonary disease group and treatment group.Animal models of COPD were induced in mice by lipopolysaccharide combined with smoke.The effects of PME on COPD model mice was analyzed by HE staining,transmission electron microscopy and the ratio of wet/dry weight of mouse lung tissue.The effects of PME on COPD model mice were analyzed by HE staining,transmission electron microscopy and the ratio of wet/dry weight of mouse lung tissue.The effects of PME on inflammatory factor tumor necrosis factor(TNF)-α,interleukin(IL)-6 and IL-1β in lung tissue were analyzed by ELISA and Western blotting.The effects of PME on oxidative stress in lung tissue were analyzed by dihydroethidium(DHE)staining and Western blotting.The effects of PME on nuclear factor kappa-B(NF-κB)pathway and nuclear factor erythroid 2-related factor 2(Nrf2)pathway were analyzed by protein immunoblotting.Results Compared with the COPD group,PME treatment could significantly improve the lung tissue injury and the number of inflammatory cells in mice,and the wet/dry weight ratio of lung tissue was significantly reduced.Compared with the control group,the levels of TNF-α,IL-6 and IL-1β in the alveolar lavage fluid of COPD mice significantly increased,and the level of TNF-α,IL-6 and IL-1β in the alveolar lavage fluid of mice after PME treatment was significantly reduced.In addition,compared with the control group,the protein expression of TNF-α,IL-6 and IL-1β in the lung tissue of COPD mice significantly increased,and the level of TNF-α,IL-6 and IL-1β in the lung tissue of COPD mice after PME treatment were significantly reduced.Immunohistochemistry and Western blotting showed that the level of superoxide dismutase 2(SOD2)protein in COPD group was significantly lower than that in control group,while PME treatment could improve the level of superoxide dismutase protein.The analysis of MDA content in lung tissue showed that compared with the COPD group,the production of MDA in lung tissue of COPD mice was significantly inhibited after PME treatment.Protein Western blotting showed that PME treatment could prevent the phosphorylation of inhibitor of NF-κB(IκBα)and the transfer of NF-κB p65 to the cell nucleus,and the expression of Nrf2 and its main downstream target heme oxygenase-1(HO-1)in the lung tissue of mice treated with PME significantly increased.Conclusion PME is able to inhibit inflammation and oxidative stress and improve lung tissues damage in the COPD model in vivo and this protection effect might be both the Nrf2 pathway activation and NF-κB pathway inhibition.

外文关键词：

PeimineChronic obstructive pulmonary diseaseInflammationOxidative damageImmunohistochemistryEnzyme-linked immunosorbent assayWestern blottingMouse

作者：

陈培、陈小菊、杜竺蔓、汪操会

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作者单位：

成都大学附属医院呼吸与危重症医学科,成都 610081

成都市金牛区营门口社区卫生服务中心全科医学科,成都 610031

关键词：

贝母素甲慢性阻塞性肺疾病炎症氧化损伤免疫组织化学酶联免疫吸附剂测定免疫印迹法小鼠

基金：

四川省卫生健康委医学科技项目四川省卫生健康委医学科技项目成都大学本科教育教学改革项目

项目编号：

川卫函[2021]366号21PJ126cdjgb2019088

出版年：

2024

DOI：

10.16098/j.issn.0529-1356.2024.02.013

解剖学报

中国解剖学会

解剖学报

CSTPCD

影响因子：0.462

ISSN：0529-1356

年,卷(期)：2024.55(2)

参考文献量19