【摘要】 目的比较乳酸乳球菌及植物乳杆菌对尘螨致变应性气道炎症小鼠的免疫调节作用,对其脾细胞MAPK通路的影响及可能机制。方法将实验小鼠分对照组(N组)、尘螨组(单纯尘螨致敏激发,M组)、尘螨+乳酸乳球菌组及尘螨+植物乳杆菌组[尘螨致敏激发同时分别用乳酸乳球菌灌胃(L组),植物乳杆菌灌胃(P组)],末次激发后3 d行肺组织病理学检查,ELISA法检测脾细胞培养上清IL-10水平,流式细胞术检测CD3+CD4+脾细胞分泌IL-4/IFNγ水平,Western blot法检测脾细胞中总的及磷酸化P38、ERK和JNK蛋白水平。结果口服乳酸菌明显减轻尘螨致敏激发导致的嗜酸细胞性气道炎症,以喂服乳酸乳球菌更显著。L组及M组脾细胞培养上清IL-10的生成显著增加(P<0.05),并以L组更明显,且其IL-10的释放率亦明显高于其余三组(P<0.05);流式细胞术显示L组和P组分泌IL-4的CD4+细胞减少的同时,总CD4+细胞比例反而增高,以L组为明显。M组与P组磷酸化P38表达水平较N组显著增高,L组与N组比较基本无变化,各组间的磷酸化ERK及JNK无明显差异。结论口服乳酸乳球菌可改善尘螨所致小鼠嗜酸粒细胞性气道炎症,其免疫调节可能与诱导CD4+调节T细胞,分泌抑制性细胞因子IL-10,下调P38 MAPK通路活性,从而下调Th2炎症相关。更多还原

【Abstract】 Objective To investigate the effects and mechanisms of lactic acid bacteria on MAPK signaling in immune response of dust mite sensitized mice.Methods Forty C57BL/6 mice in Group M,P and L, were sensitized and challenged with mite extract while then the animals in Group N were treated with saline as control.The mice in Group L and P were fed with Lactococcus lactis or Lactobacillus respectively.Three days after the last challenge,all mice were sacrificed for lung pathological examination.IL-10 level in culture supernatant of splenocytes stimulated with mite extract was detected by ELISA.The expression of IL-4/IFN-γ on CD3+CD4+ cells was detected by flow cytometry.Western blot were performed for detection of MAPK signaling(P38,ERK,and JNK) from mice’ s spleen cells stimulated with mite extract.Results The mice fed with Lactococcus lactis(Group L) had lower rate of eosinophilic airway inflammation and higher level of IL-10 in the culture supernatant of splenocytes than Group P.Meanwhile,the number of CD4+ T cell with IL-4 expression was decreased revealed by the analysis of flow cytometry.P38 signaling in spleen cells was activated in the mice of Group M,similarly in the mice of Group P,but not of Group L.Conclusion Oral treatment of Lactococcus lactis can induce an immune tolerance in response to mite by up-regulating the level of Tr cells secreting IL-10,thus inhibiting activation of P38 signaling.更多还原