白介素17在脂多糖诱导小鼠急性肝损伤中的作用

Potential mechanism of interleukin-17 on lipopolysaccharide-induced acute liver injury in mice

目的:研究白介素17(IL-17)在脂多糖(LPS)介导小鼠急性肝损伤中的可能作用机制。方法:将18只C57BL/6小鼠随机分为对照组、LPS模型组和抗IL-17干预组,先用抗IL-17腹腔注射干预组小鼠,2 h后LPS模型组和抗IL-17干预组腹腔注射LPS诱导小鼠急性肝损伤。采用全自动生化仪测定血清丙氨酸转氨酶(ALT)水平,肝组织病理学检测肝损伤程度。行流式细胞术检测小鼠肝、脾辅助T细胞17(Th17细胞)表达,蛋白质印迹法和电泳迁移率变动分析检测抗IL-17对肝内丝裂原活化蛋白激酶(MAPK)/核因子κB(NF-κB)炎症信号通路的影响。结果:LPS腹腔注射引起小鼠局灶性肝细胞坏死、炎性细胞聚集,血清ALT明显升高(P<0.05)。流式细胞术发现肝内Th-17细胞表达显著增加,蛋白质印迹法和电泳迁移分析法表明c-Jun氨基末端激酶(p-JNK)和NF-κB炎症信号通路激活。抗IL-17干预组肝损伤和血清ALT水平均较LPS模型组显著改善,肝内p-JNK和NF-κB(P65)表达下调(均P<0.05)。结论:Th17细胞通过分泌IL-17参与LPS所致脓毒症急性肝损伤和肝内炎症过程,早期应用中和性IL-17抗体可显著减轻肝损伤和肝内炎症进程。

Objective To investigate the potential mechanism underlying the effect of interleukin 17（IL-17） on lipopolysaccharide（LPS）-induced acute liver injury in mice.Methods Eighteen C57BL/6 mice were randomly divided into normal control group,LPS model group and anti-IL-17 treatment group.LPS was administered intraperitoneally to induce acute liver injury in LPS model group and anti-IL-17 treatment group.In anti-IL-17 treatment group,anti-IL-17 was given intraperitoneally 2 h before LPS administration.Histopathological examination was performed with section of liver specimen,and serum level of alanine aminotransferase（ALT） was measured.Both hepatic and splenic T help cells 17（Th17cells） were evaluated by flow cytometry.The activation of mitogen-activated protein kinase（MAPK）/nuclear transcription factor κB（NF-κB） signal pathway in liver was detected by Western blotting and electrophoretic mobility shift assay（EMSA）.Results Significant liver injury could be observed histopathologically in LPS model group with increased serum transaminase levels and upregulated hepatic Th17 cells,and c-Jun N-terminal kinase（JNK）/NF-κB signal pathway was activated.In anti-IL-17 treatment group the LPS-induced liver injury was attenuated,serum transaminase levels was decreased,and the activation of JNK/NF-κB signal pathway was inhibited.Conclusions IL-17,which is secreted by Th17 cells,is involved in the LPS-induced acute liver injury and inflammation in mice,and administration of anti-IL-17 at the early stage could ameliorate LPS-induced liver injury and inflammation.