Early gene response to hepatic ischemia/reperfusion

The purpose of this study was to define the differences in heat shock protein (hsp)70, albumin, α₁-acid glycoprotein (AGP), and CCAAT enhancer binding proteins (C/EBP) α and β mRNA between hepatic ischemia and reperfusion, and to begin to explore C/EBP protein production. These genes have been found important in the hepatic response to lipopolysaccharide and inflammation. In two experiments, Sprague-Dawley rats underwent temporary occlusion of the median and left hepatic lobe vasculature. The first experiment included a single sham-operated group and ligation of the right hepatic lobes during reperfusion. It compared 30 and 60 min ischemia to 2 h reperfusion. The second experiment included a sham-operated group for every time point, and the right hepatic lobes were not ligated during reperfusion; a 30-min ischemia group was compared to 2-, 5-, and 24-h reperfusion groups. Total RNA from the ischemic lobes was analyzed by Northern hybridization for hsp70, albumin, AGP, and C/EBPα and β. C/EBPα and β proteins were compared by Western blotting. Differences in experimental design played an important role in interpretation of results. hsp70 mRNA began to increase during ischemia. Albumin mRNA remained constant during ischemia and reperfusion. The ischemic hepatocyte nucleus is not quiescent and retains the ability to upregulate certain genes, e.g., hsp70. Changes in mRNA in response to hepatic ischemia/reperfusion occur rapidly. Hepatic ischemia/reperfusion does not recapitulate the classic acute phase response; albumin is not downregulated during reperfusion.