槲皮素通過抑制肺巨噬細胞的M1極化減輕海水吸入誘導的小鼠急性肺損傷
發(fā)布時間:2018-04-16 14:05
本文選題:急性肺損傷 + 槲皮素。 參考:《細胞與分子免疫學雜志》2017年06期
【摘要】:目的研究槲皮素對海水誘發(fā)性急性肺損傷(SW-ALI)的保護作用,并探索該作用與M1型巨噬細胞極化及其介導的炎癥的相關(guān)性。方法雄性C57BL/6小鼠隨機分成正常對照組、槲皮素處理組、SW-ALI模型組、SW-ALI聯(lián)合槲皮素治療組,每組15只。SW-ALI模型組小鼠采用10 g/L戊巴比妥鈉腹腔注射麻醉,經(jīng)口咽插管按4 mL/kg劑量勻速將海水注入肺中;SW-ALI聯(lián)合槲皮素治療組于海水注射前0.5 h給予槲皮素(200 mg/kg)腹腔注射;正常對照組、槲皮素處理組經(jīng)腹腔注射等量PBS或槲皮素。各組小鼠在造模0.5、1、2、3、4 h后,于麻醉狀態(tài)下行腹主動脈取血1 mL進行血氣分析;3 d后,取1/3肺臟制備常規(guī)冰凍切片、HE染色觀察肺組織病變;1/3肺臟稱濕質(zhì)量,80℃恒溫箱烤48 h至干質(zhì)量恒定,計算干/濕質(zhì)量比(D/W);采用Western blot法檢測肺組織中M1型巨噬細胞標志蛋白誘導型一氧化氮合酶(iNOS)的水平,實時定量PCR檢測肺組織中iNOS及腫瘤壞死因子α(TNF-α)、白細胞介素1β(IL-1β)、IL-4及IL-10的mRNA水平。結(jié)果槲皮素能明顯減輕肺組織病理改變;降低二氧化碳分壓(PaCO_2)并增加氧分壓(PaO_2)和肺組織D/W;減少iNOS蛋白水平,下調(diào)TNF-α及IL-1β的水平且上調(diào)IL-4及IL-10的mRNA水平。結(jié)論槲皮素可通過抑制M1型巨噬細胞極化及其介導的免疫反應顯著改善SW-ALI后氣體交換功能、減輕肺組織病變。
[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.
【作者單位】: 中國人民解放軍153醫(yī)院呼吸科;第四軍醫(yī)大學口腔醫(yī)院頜面外科;
【分類號】:R285.5
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