摘要目的 评价Toll样受体7(TLR7)激动剂对脓毒症小鼠肝损伤时c-jun氨基末端激酶(JNK)信号通路的影响.方法 清洁级健康雄性成年C57BL/6小鼠180只,10～14周龄,体重20～26g.采用随机数字表法分为3组(n=60):假手术组(S组)、脓毒症组(Sep组)和TLR7激动剂组(GDQ组).采用盲肠结扎穿孔法制备小鼠脓毒症模型,GDQ组制备模型前24 h时腹腔注射TLR7激动剂1.5 g/kg.分别于术后6、12和24 h时每组取10只处死取肝,采用Western blot法检测IL-6和IL-10的表达,术后24 h时采用免疫组化法检测JNK的表达,光镜下观察肝组织病理学结果.余小鼠术后14 d时观察存活情况,计算14d生存率.结果 与S组比较,Sep组和GDQ组小鼠14 d生存率降低,术后6、12和24 h时肝IL-6、IL-10和JNK表达上调(P＜0.05);与Sep组比较,GDQ组小鼠14 d生存率升高,术后6、12和24 h时肝IL-6、IL-10和JNK表达下调(P＜0.05).GDQ组肝病理学损伤较Sep组减轻.结论 TLR7激动剂可通过阻断JNK信号通路减轻脓毒症小鼠的肝损伤.

abstractsObjective To evaluate the effect of Toll-like receptor 7 (TLR7) agonist on c-Jun Nterminal kinase (JNK) signaling pathway during liver injury in the septic mice.Methods One hundred eighty pathogen-free adult male C57BL/6 mice,aged 10-14 weeks,weighing 20-26 g,were randomly divided into 3 groups (n=60 each) using a random number table:sham operation group (group S);sepsis group (group Sep);TLR7 agonist group (group GDQ).Sepsis was induced by cecum ligation and puncture.In group GDQ,TLR7 agonist 1.5 g/kg was injected intraperitoneally at 24 h before establishment of the model.At 6,12 and 24 h after operation,10 mice in each group were sacrificed,and the livers were removed to detect the expression of interleukin-6 (IL-6) and IL-10 by Western blot.The expression of JNK was determined by immuno-histochemistry,and the histopathologic changes of livers were examined with a light microscope at 24 h after operation.The survival of mice was observed at 14 days after operation,and the 14-day survival rates were calculated.Results Compared with group S,the 14-day survival rates were significantly decreased,and the expression of IL-6,IL-10 and JNK was significantly up-regulated at 6,12 and 24 h after operation in Sep and GDQ groups (P＜0.05).Compared with group Sep,the 14-day survival rates were significantly increased,and the expression of IL-6,IL-10 and JNK was significantly down-regulated at 6,12 and 24 h after operation in group GDQ (P＜0.05).The pathological changes of livers were significantly attenuated in group GDQ as compared with group Sep.Conclusion TLR7 agonist can reduce the liver injury through blocking the JNK signaling pathway in the septic mice.