论文部分内容阅读
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 possible mechanism of interleukin 17 (IL-17) in lipopolysaccharide (LPS) -mediated acute liver injury in mice. Methods: Eighteen C57BL / 6 mice were randomly divided into control group, LPS model group and anti-IL-17 intervention group. The mice in the intervention group were intraperitoneally injected with anti-IL-17. 17 intervention group intraperitoneal injection of LPS induced acute liver injury in mice. Serum alanine aminotransferase (ALT) levels were measured by automatic biochemical analyzer. Liver injury was detected by histopathology. Flow cytometry was used to detect the expression of Th17 cells in the liver and spleen of mice. Western blotting and electrophoretic mobility shift assay were used to detect the effect of anti-IL-17 on mitogen-activated protein kinase (MAPK) / nuclear factor κB (NF-κB) inflammatory signaling pathway. Results: The intraperitoneal injection of LPS caused focal necrosis of hepatocytes, accumulation of inflammatory cells and increased serum ALT (P <0.05). The expression of Th-17 cells in the liver was significantly increased by flow cytometry. Western blotting and electrophoretic mobility shift assay showed that c-Jun N-terminal kinase (p-JNK) and NF-κB activation were activated. Anti-IL-17 intervention group, liver injury and serum ALT levels were significantly improved compared with LPS model group, liver p-JNK and NF-κB (P65) expression was down (P <0.05). Conclusion: Th17 cells are involved in acute liver injury and intrahepatic inflammatory process induced by LPS by secreting IL-17. Early application of neutralizing IL-17 antibody can significantly reduce the process of liver injury and intrahepatic inflammation.