Suppression of Autophagy in Rat Liver at Late Stage of Polymicrobial Sepsis

• DOI: 10.1097/shk.0b013e31820b2f05
• Publication Date: 2011-01-25T06:15:07Z
• Authors: Wei-Shan Chien; Yen-Hsu Chen; Pei-Chi Chiang; Hsiu-Wen Hsiao; Shu-Mien Chuang; Sheng-I Lue; Chin Hsu
• Keywords: Proinflammatory cytokine; Autophagosome; Homeostasis

Sepsis develops as a result of the host response to infection, and its mortality rate in ICU remains high. Severe inflammation usually causes overproductions proinflammatory cytokines, i.e., TNF-α reactive oxygen species, which lead mitochondrial damage energetic depletion. Autophagy is survival mechanism for eukaryote recycle intracellular nutrients maintain energy homeostasis. We hypothesize that autophagy plays beneficial role pathogenesis organ failure during sepsis. A rat model cecal ligation puncture (CLP) simulate peritonitis-induced sepsis was used, indicators liver dysfunction, serum glutamic oxaloacetic, pyruvic, alkaline phosphatase, bilirubin were measured. Levels LC3-II LC3 aggregation quantified by Western blot analysis immunohistochemistry, respectively. The tissue localization identified immunohistochemistry transmission electron microscopy. Our results showed (a) increase level occurs at 3 h, peaks 6 then surprisingly declines quickly until 18 h after CLP (CLP18h); (b) significant hepatic dysfunction observed CLP18h; (c) ratio significantly higher hepatocytes than Kupffer cells, (d) loss Atg7, an essential gene autophagosome formation, exaggerates TNF-α-induced cell death, depletion ATP, decrease albumin production hepatocytes. These indicate transiently early stage, decline late stage may contribute functional polymicrobial