槲皮素通过抑制肺巨噬细胞的M1极化减轻海水吸入诱导的小鼠急性肺损伤
发布时间:2018-04-16 14:05
本文选题:急性肺损伤 + 槲皮素 ; 参考:《细胞与分子免疫学杂志》2017年06期
【摘要】:目的研究槲皮素对海水诱发性急性肺损伤(SW-ALI)的保护作用,并探索该作用与M1型巨噬细胞极化及其介导的炎症的相关性。方法雄性C57BL/6小鼠随机分成正常对照组、槲皮素处理组、SW-ALI模型组、SW-ALI联合槲皮素治疗组,每组15只。SW-ALI模型组小鼠采用10 g/L戊巴比妥钠腹腔注射麻醉,经口咽插管按4 mL/kg剂量匀速将海水注入肺中;SW-ALI联合槲皮素治疗组于海水注射前0.5 h给予槲皮素(200 mg/kg)腹腔注射;正常对照组、槲皮素处理组经腹腔注射等量PBS或槲皮素。各组小鼠在造模0.5、1、2、3、4 h后,于麻醉状态下行腹主动脉取血1 mL进行血气分析;3 d后,取1/3肺脏制备常规冰冻切片、HE染色观察肺组织病变;1/3肺脏称湿质量,80℃恒温箱烤48 h至干质量恒定,计算干/湿质量比(D/W);采用Western blot法检测肺组织中M1型巨噬细胞标志蛋白诱导型一氧化氮合酶(iNOS)的水平,实时定量PCR检测肺组织中iNOS及肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、IL-4及IL-10的mRNA水平。结果槲皮素能明显减轻肺组织病理改变;降低二氧化碳分压(PaCO_2)并增加氧分压(PaO_2)和肺组织D/W;减少iNOS蛋白水平,下调TNF-α及IL-1β的水平且上调IL-4及IL-10的mRNA水平。结论槲皮素可通过抑制M1型巨噬细胞极化及其介导的免疫反应显著改善SW-ALI后气体交换功能、减轻肺组织病变。
[Abstract]:Objective to study the effects of quercetin on acute lung injury induced by seawater (SW-ALI) protective effect, and explore the correlation function and inflammation in the M1 type macrophage polarization and its mediated. Methods male C57BL/6 mice were randomly divided into normal control group, quercetin group, SW-ALI model group, SW-ALI combined with quercetin treatment group, 15 rats in each group.SW-ALI model group 10 g/L mice by intraperitoneal injection of pentobarbital sodium anesthesia, oropharyngeal intubation at a dosage of 4 mL/kg uniform pumping seawater into the lungs; SW-ALI combined with quercetin treatment group in seawater before injection was given 0.5 h quercetin (200 mg /kg) intraperitoneal injection; control group, quercetin group by intraperitoneal injections of PBS or quercetin. Mice in each group model 0.5,1,2,3,4 h after anesthesia in abdominal aorta blood gas analysis of 1 mL; 3 D, 1/3 lung routine preparation of frozen sections, observe the pathological changes of lung tissue HE staining 1/3; lung wet weight of 80 h to 48 DEG thermostat baked dry mass is constant, calculation of dry / wet mass ratio (D/W); type M1 in lung tissue was detected by Western blot method in the macrophage marker protein of inducible nitric oxide synthase (iNOS) levels, iNOS and tumor necrosis factor alpha real-time quantitative PCR detection of lung organization (TNF-), interleukin 1 beta (IL-1 beta), IL-4 and IL-10. The mRNA level of quercetin can significantly reduce the pathological changes of lung tissue; reduce carbon dioxide partial pressure (PaCO_2) and the increase of oxygen partial pressure (PaO_2) and D/W in lung tissue; reduce the protein level of iNOS, down-regulation of TNF- and alpha IL-1 beta level and up regulation of IL-4 and IL-10 mRNA level. Conclusion quercetin can gas exchange function by suppressing the immune response to M1 mediated macrophage polarization and significantly improve the SW-ALI, reduce the lung tissue lesions.
【作者单位】: 中国人民解放军153医院呼吸科;第四军医大学口腔医院颌面外科;
【分类号】:R285.5
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