von Allmen D, Li S J, Hasselgren P O, Fischer J E
Department of Surgery, University of Cincinnati Medical Center, Ohio 45267.
Surg Gynecol Obstet. 1991 Jun;172(6):441-8.
The effect of ischemia on hepatic protein synthesis during sepsis is not known, but is of clinical relevance, since hepatic blood flow decreases during the late phase of sepsis. In this study, synthesis of acute-phase proteins was measured in perfused livers of rats 16 hours after sham operation or cecal ligation and puncture. Livers from each group had 45 minutes of complete ischemia or control perfusion. Protein synthesis was measured during two hour perfusion after the ischemia or control period, by determining incorporation of 3H-leucine into total secreted trichloracetic acid precipitated proteins, immunoprecipitated complement component C3 and albumin and phosphotungstenate-precipitated alpha 1-acid glycoprotein. Lactate, glutamine-oxalacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) levels in the perfusate were measured during preischemic and postischemic perfusion. Tissue glutathione levels were measured at the end of the perfusion. Synthesis of alpha 1-acid glycoprotein was increased by 100 per cent and albumin synthesis decreased by 46 per cent in septic livers, consistent with an acute-phase response and apparent downregulation of albumin synthesis during early sepsis. Synthesis rates were reduced by 50 to 60 per cent after ischemia in perfused livers from sham operated rats and 70 to 80 per cent in livers from septic rats. Hepatic production of interleukin-1 was not different between the groups during perfusion. GOT and GPT levels increased significantly during ischemia of both nonseptic and septic livers and rapidly returned toward baseline during reperfusion. Lactate levels were higher in perfusate of septic than of nonseptic livers before ischemia and increased further during ischemia. The results suggest that ischemia inhibits production of secreted hepatic proteins similarly in nonseptic and septic livers, but perhaps to a slightly greater extent in septic livers.
缺血对脓毒症期间肝脏蛋白质合成的影响尚不清楚，但具有临床相关性，因为在脓毒症晚期肝血流量会减少。在本研究中，对假手术或盲肠结扎穿孔术后16小时的大鼠灌注肝脏中急性期蛋白的合成进行了测定。每组肝脏进行45分钟的完全缺血或对照灌注。在缺血或对照期后的两小时灌注期间，通过测定3H-亮氨酸掺入总分泌的三氯乙酸沉淀蛋白、免疫沉淀的补体成分C3和白蛋白以及磷钨酸盐沉淀的α1-酸性糖蛋白中，来测量蛋白质合成。在缺血前和缺血后灌注期间，测量灌注液中的乳酸、谷草转氨酶（GOT）和谷丙转氨酶（GPT）水平。在灌注结束时测量组织谷胱甘肽水平。脓毒症肝脏中α1-酸性糖蛋白的合成增加了100%，白蛋白合成减少了46%，这与急性期反应以及脓毒症早期白蛋白合成的明显下调一致。假手术大鼠灌注肝脏缺血后合成率降低了50%至60%，脓毒症大鼠肝脏中降低了70%至80%。灌注期间两组间肝脏白细胞介素-1的产生没有差异。非脓毒症和脓毒症肝脏缺血期间GOT和GPT水平均显著升高，再灌注期间迅速恢复至基线水平。缺血前脓毒症肝脏灌注液中的乳酸水平高于非脓毒症肝脏，缺血期间进一步升高。结果表明，缺血对非脓毒症和脓毒症肝脏中分泌性肝脏蛋白产生的抑制作用相似，但在脓毒症肝脏中可能略大。
