【摘要】 目的观察短链脂肪酸(SCFA)作用下伤寒沙门菌能否诱导巨噬细胞凋亡及其机制。方法将伤寒沙门菌及SCFA作用菌与巨噬细胞共孵育,于2、4、8、12和24h后,用流式细胞术检测细胞凋亡率,并于作用8h后检测NO、TNF-α、caspase-3产生量,及加入TNF-α抗体和caspase-3抑制剂后的细胞凋亡率。结果SCFA作用下的伤寒沙门菌可诱导巨噬细胞凋亡,凋亡率与对照组及伤寒沙门菌原菌组比较差异有统计学意义(P<0.01);作用8h后NO、TNF-α、caspase-3的产生量均高于对照组(P<0.01);加入TNF-α抗体后凋亡率明显降低(P<0.01)。结论SCFA作用下伤寒沙门菌可诱导巨噬细胞凋亡,其凋亡可能由活性氮及细胞因子TNF-α介导和caspase-3参与。更多还原

【Abstract】 Objective To study the apoptosis of macrophages induced by SCFA-stressed Salmonella typhi and the mechanism of this apoptosis.Methods The apoptosis of macrophages infected with S.typhi and its SCFA-stressed form was determined by flow cytometry at different times 2,4,8,12 and 24 hours after infection.To study the mechanism of this apoptosis,NO,tumour necrosis factor-α(TNF-α) and caspase-3 were detected in the macrophages 8 hours after infection with S.typhi and its SCFA-stressed form,and apoptosis rates were determined by flow cytometry after TNF-α antibody and caspase-3 inhibitor were respectively added to the macrophages.Results SCFA-stressed S.typhi induced apoptosis in significantly more macrophages than in cells grown under normal conditions(P<0.01).Significantly increased production of reactive nitrogen intermediates and caspase-3 activity during macrophage apoptosis induced by SCFA-stressed S.typhi correlated with the increased production of TNF-α(P<0.01).Apoptosis rates of macrophages were significantly inhibited by the TNF-α antibody and caspase-3 inhibitor(P<0.01).Conclusion The results indicate that reactive nitrogen intermediates and TNF-α induce caspase-3 mediated apoptosis of macrophages by S.typhi in the presence of SCFA.These findings may be relevant for a better understanding of the interaction between Salmonella and macrophages and may be of clinical importance in the development of preventive interventions to treat the infection.更多还原