Role of Glycogenolytic and Innate Immunological Markers during Lethal and Sublethal Sepsis in Experimental Animal Model

• Main Authors: Che Lin, 林喆
• Other Authors: Ching-Yuang Lin
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/26311154416873972573

碩士 === 長榮大學 === 醫學研究所 === 95 === We focused on the hypothesis that rebound hypoglycemia with activating MyD88-independent pathway are required for the survival of lethal hypoglycemia in sepsis. Forty-eight mice (BALB/c) were divided into three groups (control, sublethal, and lethal group). The results showed that at 6 hours sublethal dose E. coli (0.1LD) decreased blood glucose as the same as lethal dose E. coli (10LD). The blood insulin concentrations were significantly higher at 6 hours (P<0.05) in the sublethal group compared with those in the lethal group. Liver G6Pase activity levels rebounded with blood glucose at 3 days and 7 days in the sublethal group. The sublethal group induced the greatest fold increase of liver G6Pase activity at 3 days. Liver G6PT mRNA measured by realtime PCR revealed liver G6PT levels were lower at 6 hours in the sublethal group compared with those in the lethal group. The sublethal group induced the greatest fold increase of liver G6PT mRNA at 7 days. Liver TRAM mRNA measured by realtime PCR revealed liver TRAM levels were higher at 6 hours in the sublethal group compared with those in the lethal group. The sublethal group induced the greatest fold increase of liver G6PT mRNA at 3 days. These results indicated that the lethal group reduced TRAM production and subsequent expression of IRF-3 and IFN-beta proteins in liver IHC. The increase in NF-kappaB protein was accounted for by western blot in the sublethal group and compared with those in the lethal group at 6 hours. The level of NF-kappaB protein increased 6 hours through 7days progressively in the sublethal group. The increase in IRF-3 protein was accounted for by western blot in the sublethal group and compared with those in the lethal group. The level of IRF-3 protein increased progressively from 6 hours to 7 days in the sublethal group. The levels of IRF-3 in lethal group were lower than those of control group. The sublethal group induced the greatest increase of liver IFN-beta protein at 3 days. This data suggests that lethal dose E. coli reduces activation of IFN-beta. Interestingly, blood insulin decrease was synchronic with IFN-beta decrease. Finally, compared with a sublethal dose of E. coli ATCC 25922, sepsis induced by a lethal dose causes blood insulin decrease, liver G6PT mRNA expression increase, liver TRAM mRNA expression and protein decrease, liver NF-kappaB protein decrease, liver IRF-3 protein decrease, and liver IFN-beta protein decrease.