N-乙酰-L-半胱氨酸对多器官功能障碍综合征模型小鼠肺树突细胞损伤的保护作用

目的 探讨抗氧化剂N-乙酰-L-半胱氨酸(NAC)对酵母多糖诱导的多器官功能障碍综合征(MODS)模型肺树突细胞(DCs)损伤的保护作用.方法 健康雄性BALB/c小鼠腹腔注射酵母多糖复制MODS模型,随机分为对照组、酵母多糖组、酵母多糖+NAC组(n=20).建模后48h处死动物,采用生化法检测肺组织髓过氧化物酶(MPO)活性；光镜下观察肺组织病理学变化；采用密度梯度离心及CDllc+免疫磁珠分离肺DCs,流式细胞术检测DCs表面MHC-Ⅱ/Ⅰ-Ad分子及共刺激分子CD86的表达；Annexin V/7-AAD双染色流式细胞术检测DCs凋亡情况.结果 与对照组比较,酵母多糖组肺组织MPO活性显著升高(P＜0.05),肺组织损伤明显,可见大量中性粒细胞浸润,肺DCs表面MHC-Ⅱ/Ⅰ-Ad、CD86阳性表达及细胞凋亡比例均显著增高(P＜0.05).与酵母多糖组比较,酵母多糖+NAC组肺组织MPO活性明显下降(P＜0.05),肺损伤程度减轻,中性粒细胞浸润减少,肺DCs表面MHC-Ⅱ/Ⅰ-Ad、CD86阳性表达及细胞凋亡比例显著下降(P＜0.05).结论 NAC可以减轻MODS模型小鼠的肺损伤,抑制肺DCs活化诱导的细胞凋亡,对肺DCs损伤具有保护作用.

Protective effect of N-acetylcysteine on lung dendritic cells against damage in multiple organ dysfunction syndrome model

Objective To explore the protective effect of N-acetylcysteine(NAC) on lung dendritic cells(DCs) from damage in multiple organ dysfunction syndrome(MODS) in mouse model.Methods Animal model of MODS was reproduced by injecting zymosan into the peritoneal cavity of BALB/c mice,and the mice were thereafter randomly divided into zymosan group,zymosan + NAC group and control group,20 for each group.Myeloperoxidase MPO activity in lung tissue was measured by biochemical analysis 48 hours after modeling.Pathological changes of the lung were observed under light microscope.Lung DCs were isolated by density gradient centrifugation and CD11c+ immunomagnetic beads.DCs’ phenotypes of MHC-Ⅱ/ⅠAd and CD86 were analyzed by flow cytometry.Apoptosis of DCs was detected by flow cytometry with double labeling of Annexin V and 7-AAD.Results Compared with control group,the MPO activity in lung tissue remarkably increased in zymosan group(P<0.05).Infiltration with a large number of neutrophilic granulocytes was found in lungs,suggesting serious inflammation and injuries in lung.The expressions of MHC-Ⅱ/Ⅰ-Ad and CD86 on DC surface and the percentage of DC apoptosis increased dramatically(P<0.05).Compared with zymosan group,the MPO activity was remarkably lowered and the lung injury was alleviated(P<0.05);the number of infiltrating neutrophilic granulocytes markedly decreased,and the expressions of MHC-Ⅱ/Ⅰ-Ad and CD86 on the DC surface and the percentage of DC apoptosis were mitigated dramatically(P<0.05) in zymosan + NAC group.Conclusion NAC in vivo could inhibit DC activation-induced apoptosis and relieve lung injury,thus it possesses protective effect on lung DCs against damage in MODS model.