EARLY GENE RESPONSE TO HEPATIC ISCHEMIA REPERFUSION/

The purpose of this study was to define the differences in heat shock protein (hsp)70, albumin, alpha(1)-acid glycoprotein (AGP), and CCAAT enhancer binding proteins (C/EBP) alpha and beta mRNA between hepatic ischemia and reperfusion and to begin to explore C/EBP protein product ion. These genes have been found important in the hepatic response to lipopolysaccharide and inflammation, In two experiments, Sprague-Dawle y rats underwent temporary occlusion of the median and left hepatic lo be vasculature. The first experiment included a single sham-operated g roup and ligation of the right hepatic lobes during reperfusion. It co mpared 30 and 60 min ischemia to 2 h reperfusion, The second experimen t included a sham-operated group for every time point, and the right h epatic lobes were not Ligated during reperfusion; a 3O-min ischemia gr oup was compared to 2-, 5-, and 24-h reperfusion groups, Total RNA fro m the ischemic lobes was analyzed by Northern hybridization for hsp70, albumin, AGP, and C/EBP alpha and beta, C/EBP alpha and beta proteins were compared by Western blotting. Differences in experimental design played an important role in interpretation of results, hsp70 mRNA beg an to increase during ischemia. Albumin mRNA remained constant during ischemia and reperfusion. The ischemic hepatocyte nucleus is not quies cent and retains the ability to upregulate certain genes, e.g., hsp70. Changes in mRNA in response to hepatic ischemia/reperfusion occur rap idly. Hepatic ischemia/reperfusion does not recapitulate the classic a cute phase response; albumin is not downregulated during reperfusion. (C) 1996 Academic Press, Inc.