银杏叶提取物通过调控p38 MAPK/MLCK信号通路对高氧诱导的急性肺损伤小鼠肠黏膜屏障的保护作用OA
Effect of Ginkgo biloba extract on the intestinal mucosal barrier by regulating the p38 MAPK/MLCK signaling pathway in mice with hyperoxia-induced acute lung injury
目的 探讨银杏叶提取物(GBE)通过p38丝裂原活化蛋白激酶(MAPK)/肌球蛋白轻链激酶(MLCK)信号通路,对高氧诱导的急性肺损伤(ALI)小鼠肠黏膜屏障的保护作用.方法 将 C57BL/6J 小鼠随机分为对照组、ALI组、低剂量GBE组、高剂量GBE组和高剂量GBE+茴香菌素(anisomycin)组,每组10只.测定小鼠氧分压(PaO2)、二氧化碳分压(PaCO2)以及肺湿重与干重比值(W/D);组织学染色观察肺和小肠组织病理变化并评分;酶联免疫吸附试验检测血清炎性细胞因子、D-乳酸(D-LA)和小肠sIgA 水平;Western blotting检测相关蛋白表达.结果 与对照组相比,ALI组小鼠PaO2及闭合蛋白(occludin)、密封蛋白(claudin)、闭合小带蛋白1(ZO-1)蛋白表达水平显著降低(P<0.05),PaCO2、W/D、肺和小肠病理评分、炎性细胞因子、D-LA、DAO、sIgA水平以及p-p38 MAPK/p38 MAPK和MLCK蛋白表达水平显著升高(P<0.05).与ALI组比,低剂量GBE组和高剂量GBE组上述指标呈相反变化,且高剂量GBE组改善更显著.而高剂量GBE+anisomycin组与高剂量GBE组比较,治疗作用显著减弱(P<0.05).结论 GBE可能通过调控p38 MAPK/MLCK信号通路,减轻炎症反应,并升高肠黏膜屏障相关蛋白的表达水平,对肠黏膜屏障发挥保护作用.
Objective To explore the effects of Ginkgo biloba extract(GBE)on the intestinal mucosal barrier in mice with hyperoxia-induced acute lung injury(ALI)via the p38 mitogen-activated protein kinase(MAPK)/myosin light chain kinase(MLCK)signaling pathway.Methods C57BL/6J mice were randomly divided into control,ALI,low-dose GBE,high-dose GBE,and high-dose GBE+anisomycin,with 10 mice in each group.Oxygen partial pressure(PaO2),carbon dioxide partial pressure(PaCO2),and the ratio of lung wet weight to dry weight(W/D)were measured.Histological staining was used to observe and score pathological changes in the lung and intestinal tissues.Serum inflammatory cytokines,D-lactic acid(D-LA),and intestinal sIgA levels were detected using an enzyme-linked immunosorbent assay.The expression of related proteins was assessed by Western blotting.Results Compared with the control group,the ALI group showed significantly decreased PaO2 and expression of occludin,claudin,and zonula occludens-1(ZO-1)proteins(P<0.05),while PaCO2,W/D,lung and intestinal pathological scores,inflammatory cytokines,D-LA,diamine oxidase(DAO),sIgA levels,and p-p38 MAPK/p38 MAPK and MLCK protein expression were significantly increased(P<0.05).Compared with the ALI group,the low-and high-dose GBE groups exhibited opposite changes,with more pronounced improvements in the high-dose GBE group.The high-dose GBE+anisomycin group showed significantly attenuated therapeutic effects compared to the high-dose GBE group(P<0.05).Conclusion GBE may protect the intestinal mucosal barrier by regulating the p38 MAPK/MLCK signaling pathway,reducing inflammation,and increasing the expression levels of intestinal mucosal barrier-related proteins.
何英;邢周雄;程云;耿争光;付豹;傅小云
遵义医科大学附属医院 重症医学科,贵州 遵义 563000遵义医科大学附属医院 重症医学科,贵州 遵义 563000遵义医科大学附属医院 急诊科,贵州 遵义 563000遵义医科大学附属医院 重症医学科,贵州 遵义 563000遵义医科大学附属医院 重症医学科,贵州 遵义 563000遵义医科大学附属医院 重症医学科,贵州 遵义 563000
医药卫生
银杏叶提取物高氧急性肺损伤肠黏膜屏障p38 MAPK/MLCK炎症
Ginkgo biloba extracthyperoxiaacute lung injuryintestinal mucosal barrierp38 MAPK/MLCKinflammation
《中国医科大学学报》 2026 (2)
127-132,6
贵州省科技计划(黔科合支撑[2022]一般179)遵义市科技计划(遵市科合HZ字(2023)207号)
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