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目的:建立LPS(脂多糖)诱导的急性肺损伤小鼠模型，探究麻杏石甘汤对急性肺损伤的保护作用及机制。方法:将C57BL/6雄性小鼠随机分为正常对照组、模型对照组、麻杏石甘汤5.4、54、108 g/kg组和哌非尼酮200 mg/kg组，每组10只，连续灌胃给予相应药物或去离子水7 d,第8 d注射LPS建立急性肺损伤模型，从肺功能检测、肺部CT检测、脏器指数、肺组织病理学检查、肺组织湿/干质量比(W/D)、血清及肺灌注洗液(BLAF)中肿瘤坏死因子α(TNF-α)、白介素1β(IL-1β)、IL-6含量测定、肺组织氧化应激指标变化等综合探讨麻杏石甘汤对LPS诱导的急性肺损伤小鼠的保护作用机制。结果:与正常对照组比较，模型对照组肺灌洗液和血清中TNF-α、IL-1β、IL-6含量，肺组织病理学产生变化，肺功能指标明显改变、CT异常、肺指数显著增加，炎症因子明显增加，氧化指标明显异常，成功建立急性肺损伤模型(P<0.05或P<0.01);麻杏石甘汤能明显或部分改善模型小鼠肺部炎性细胞浸润，改善肺功能和肺部CT,能明显降低LPS诱导的急性肺损伤模型小鼠中肺组织的丙二醛(MDA)的含量，同时也能增强急性肺损伤小鼠肺组织中的超氧化物歧化酶(SOD)和还原型谷胱甘肽(GSH)的活力，还能降低血清和BLAF中IL-1β、IL-6以及TNF-α等细胞炎症因子的含量，下调肺组织p38MAPK、JNK、ERK1/2、TNF-α、IL-6蛋白的表达(P<0.05或P<0.01)。结论:麻杏石甘汤可能通过抗氧化应激、抑制相关炎症因子、调节炎症MAPK/NF-κB通路等多种途径有效预防急性肺损伤。
Abstract：Objective:To explore the protective effect and mechanism of Maxing Shigan Decoction(麻杏石甘汤) on acute lung injury(ALI) by establishing the lipopolysaccharide(LPS)-induced ALI mouse model. Methods:C57BL/6 male mice were randomly divided into normal control group, model control group, Maxing Shigan Decoction 5.4 g/kg, 54 g/kg and 108 g/kg groups, and pirfenidone 200 mg/kg group, with 10 in each group. The mice were intragastrically administrated with corresponding drugs or deionized water for 7 consecutive days, and injected with LPS on the 8th day to establish the ALI model. The protective mechanism of Maxing Shigan Decoctio on LPS-induced ALI in mice was comprehensively discussed from the aspects of lung function, lung CT,organ index, lung histopathology, wet-to-dry weight ratio(W/D) of lung tissue, contents of inflammatory factors tumor necrosis factor alpha(TNF-α),interleukin-1β(IL-1β),and IL-6 in serum and bronchoalveolar lavage fluid(BLAF),and oxidative stress indexes in lung tissue. Results:Compared with the normal control group, the model control group presented changes in the contents of inflammatory factors(TNF-α,IL-1β,IL-6) and lung histopathology, which suggested the ALI model was successfully established(P<0.05 or P<0.01). Maxing Shigan Decoction markedly or partially improved the inflammatory cell infiltration in the lungs of ALI model mice, significantly decreased the content of malondialdehyde(MDA) in lung tissue, increased the activities of superoxide dismutase(SOD) and glutathione(GSH) in lung tissue, inhibited the contents of IL-1β,IL-6,and TNF-α in serum and BLAF,and down regulated the expressions of p38 MAPK,JNK,ERK1/2,TNF-α,and IL-6 proteins(P<0.05 or P<0.01). Conclusion:Maxing Shigan Decoction has a desirable preventive impact on ALI,and its mechanism may be related to anti-oxidative stress, inhibition of associated inflammatory factors, and modulation of multiple inflammatory pathways such as MAPK/NF-κB pathway.
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基本信息:
DOI：10.13412/j.cnki.zyyl.20230220.002
中图分类号:R285.5
引用信息:
[1]侯雯倩,刘东玲,海洋,等.麻杏石甘汤通过调节MAPK/NF-κB通路缓解LPS致急性肺损伤的炎症反应[J].中药药理与临床,2023,39(03):1-7.DOI:10.13412/j.cnki.zyyl.20230220.002.
基金信息:
国家自然科学基金面上项目(编号：82074419); 甘肃省教育厅“双一流”科研重点项目(编号：GSSYLXM-05)
2023-02-21
2023-02-21
2023-02-21