摘要目的 探讨脓毒症小鼠肝损伤时FUNDC1/微管相关蛋白l轻链3Ⅱ(LC3Ⅱ)信号通路的变化.方法 清洁级健康成年雄性C57BL/6小鼠32只,6周龄,体重20～25 g,采用随机数字表法分为2组:假手术组(n=8)和脓毒症组(n=24).采用盲肠远端结扎穿孔法制备小鼠脓毒症模型.假手术组于造模后24 h、脓毒症组分别于造模后6、12和24h时,摘眼球取血样,测定血清AST和ALT的浓度;然后处死小鼠,取肝右叶组织,进行病理学损伤评分,采用Western bolt法检测FUNDC1和LC3Ⅱ的表达水平.提取肝右叶组织线粒体,检测线粒体呼吸功能,计算线粒体呼吸控制率.结果 与假手术组比较,脓毒症组造模后各时点血清ALT和AST浓度、肝组织病理学损伤评分升高,线粒体呼吸控制率降低,FUNDC1表达下调,LC3Ⅱ表达上调(P＜0.05).结论 脓毒症诱发小鼠肝损伤的机制可能与抑制FUNDC 1/LC3Ⅱ信号通路激活有关.

abstractsObjective To investigate the changes in FUNDC1/microtubule-associated protein 1 light chain 3 Ⅱ (LC3 Ⅱ) signaling pathway during sepsis-induced liver injury in mice.Methods Tbirtytwo clean-grade healthy male C57BL/6 mice,aged 6 weeks,weighing 20-25 g,were divided into sham operation group (n =8) and sepsis group (n =24) using a random number table method.Sepsis was induced by cecal ligation and puncture.Blood samples were obtained at 24 h after operation in sham operation group and at 6,12 and 24 h after establishing the model in sepsis group for determination of concentrations of alanine aminotransferase and aspartate aminotransferase in serum.Mice were then sacrificed,and the right lobe of livers was removed for examination of the pathological changes and for determination of the expression of FUNDC1 and LC3 Ⅱ by Western blot.The mitochondria in the right lobe of livers were isolated to measure the respiratory function,and respiratory control rate was calculated.Results Compared with sham operation group,the concentrations of alanine aminotransferase and aspartate aminotransferase in serum and pathological scores were significantly increased,the respiratory control rate of mitochondria was decreased,the expression of FUNDC1 was down-regulated,and the expression of LC3 Ⅱ was up-regulated at each time point after establishing the model in sepsis group (P＜0.05).Conclusion The mechanism by which sepsis induces liver injury may be related to inhibiting activation of FUNDC1/LC3 Ⅱ signaling pathway in mice.