目的:探讨金桔精油(KEO)对脂多糖(LPS)诱导的急性肺损伤(ALI)小鼠的保护作用及机制.方法:将72例昆明雄性小鼠随机分为6组:对照组、LPS组、地塞米松(DXMS)组、低剂量KEO(KEOL)组、中剂量KEO(KEOM)组和高剂量KEO(KEOH)组,每组12只.连续灌胃给药7d后,除对照组外,其他各组小鼠均通过腹腔注射LPS(10 mg/kg)复制ALI模型.计算肺湿重与体重的比值(LW/BW).光镜下观察肺组织病理学改变.采用免疫组织化学染色法检测肺组织中肿瘤坏死因子(TNF)-α和连接蛋白(Cx)-43的表达,酶联免疫吸附试验(ELISA)法检测血清白细胞介素(IL)-1β和IL-6水平,Western blotting法测定核因子(NF)-κB p65、IκBα、p38丝裂原活化蛋白激酶(MAPK)磷酸化水平及诱导型一氧化氮合酶(iNOS)和环氧合酶(COX)-2蛋白表达量.结果:KEO预处理可显著改善LPS诱导的肺组织病理学改变.与LPS组相比,KEOM和KEOH组LW/BW比值、TNF-α、Cx-43、COX-2和iNOS蛋白表达量以及血清IL-6和IL-1β水平均明显降低(均P＜0.05).同时,不同剂量KEO组磷酸化(p)-p38,p-p65和p-IκBα表达下调(P＜0.05),以KEOH组最为显著.结论:KEO对LPS诱导的小鼠ALI有保护作用,其机制可能与阻断p38MAPK和NF-κB信号通路和减轻炎症反应有关.%Objective:To investigate the effect and mechanisms of kumquat essential oil (KEO) on lipopolysaccharide (LPS)-induced acute lung injury (ALl) in mice.Methods:Seventytwo Kunming male mice were randomly divided 6 groups (n =12 each):control group,LPS group,dexamethasone (DXMS) group,low-dose KEO (KEOL) group,mediumdose KEO (KEOM) group,and high-dose KEO (KEOH)group.After 7 days of gavage administration,the mice were subjected to ALI except for the control group.The ALI model was established by intraperitoneally injection with LPS (10 mg/kg).The lung-to-body weight ratio was calculated.The pathological changes of lung tissues were observed under light microscope.The protein expressions of tumor necrosis factor (TNF)-α and connexin (Cx)-43 in lung tissues were determined by immunohistochemistry.The levels of interleukin (IL)-1β and IL-6 in serum were measured by enzyme linked immunosorbent assay (ELISA).The p38 mitogen-activated protein kinase (MAPK),nuclear factor (NF)-κB p65,IκBα,inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 expressions were detected by western blotting.Results:LPS-induced histological alterations in lung tissues were prevented by pretreatment of KEO.Compared with the LPS group,the lung-to-body weight ratio,the expression levels of TNF-α,Cx-43,COX-2 and iNOS as well as the serum concentrations of IL-6 and 1L-1β were decreased in KEOM and KEOH groups (P＜0.05).The expression of phosphorylated (p)-p38,p-p65,and p-IκBα was down-regulated in different doses of KEO groups (P ＜ 0.05),and that was even more marked in KEOH group.Conclusion:KEO exerted a protective effect on LPS-induced ALI in mice,which might be related to blocking the p38 MAPK and NF-κB signaling pathways and reducing the inflammatory response.
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