脓毒症小鼠肝损伤时FUNDC1/LC3Ⅱ信号通路的变化

被引：4

作者：

闫梦莹

王妍妍

毛幸

冯竞成

王国林

谢克亮

于泳浩

机构：

[1] 天津医科大学总医院麻醉科天津市麻醉学研究所

来源：

中华麻醉学杂志 | 2018年 / 38卷 / 06期

关键词：

脓毒症; 肝; 膜蛋白质类; 自噬;

D O I：

暂无

中图分类号：

R459.7 [急症、急救处理];

学科分类号：

100231 [临床病理学];

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24 h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FUNDC1/LC3Ⅱ信号通路激活有关。

引用

收藏

相关论文

共 11 条

[1]

Liver - guardian, modifier and target of sepsis [J].

Strnad, Pavel ;

Tacke, Frank ;

Koch, Alexander ;

Trautwein, Christian .

NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, 2017, 14 (01) :55-66

[2]

Hypoxic mitophagy regulates mitochondrial quality and platelet activation and determines severity of I/R heart injury [J].

Zhang, Weilin ;

Ren, He ;

Xu, Chunling ;

Zhu, Chongzhou ;

Wu, Hao ;

Liu, Dong ;

Wang, Jun ;

Liu, Lei ;

Lu, Wei ;

Ma, Qi ;

Du, Lei ;

Zheng, Ming ;

Zhang, Chuanmao ;

Liu, Junling ;

Chen, Quan .

[3]

Severe Sepsis and Septic Shock [J].

Angus, Derek C. ;

van der Poll, Tom .

NEW ENGLAND JOURNAL OF MEDICINE, 2013, 369 (09) :840-851

[4]

Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells [J].

Liu, Lei ;

Feng, Du ;

Chen, Guo ;

Chen, Ming ;

Zheng, Qiaoxia ;

Song, Pingping ;

Ma, Qi ;

Zhu, Chongzhuo ;

Wang, Rui ;

Qi, Wanjun ;

Huang, Lei ;

Xue, Peng ;

Li, Baowei ;

Wang, Xiaohui ;

Jin, Haijing ;

Wang, Jun ;

Yang, Fuquan ;

Liu, Pingsheng ;

Zhu, Yushan ;

Sui, Senfang ;

Chen, Quan .

NATURE CELL BIOLOGY, 2012, 14 (02) :177-185

[5]

Heme Oxygenase-1-Mediated Autophagy Protects Against Hepatocyte Cell Death and Hepatic Injury from Infection/Sepsis in Mice [J].

Carchman, Evie H. ;

Rao, Jayashree ;

Loughran, Patricia A. ;

Rosengart, Matthew R. ;

Zuckerbraun, Brian S. .

HEPATOLOGY, 2011, 53 (06) :2053-2062

[6]

Immunodesign of experimental sepsis by cecal ligation and puncture [J].

Rittirsch, Daniel ;

Huber-Lang, Markus S. ;

Flierl, Michael A. ;

Ward, Peter A. .

NATURE PROTOCOLS, 2009, 4 (01) :31-36

[7]

Capacity of oxidative phosphorylation in human skeletal muscle.[J].Erich Gnaiger.International Journal of Biochemistry and Cell Biology.2009, 10

[8]

Autophagy in the pathogenesis of disease [J].

Levine, Beth ;

Kroemer, Guido .

CELL, 2008, 132 (01) :27-42

[9]

Management of sepsis in patients with liver failure [J].

Canabal, Juan M. ;

Kramer, David J. .

CURRENT OPINION IN CRITICAL CARE, 2008, 14 (02) :189-197

[10]

p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy [J].

Pankiv, Serhiy ;

Clausen, Terje Hoyvarde ;

Lamark, Trond ;

Brech, Andreas ;

Bruun, Jack-Ansgar ;

Outzen, Heidi ;

Overvatn, Aud ;

Bjorkoy, Geir ;

Johansen, Terje .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (33) :24131-24145