Tiao G, Noguchi Y, Lieberman M A, Fischer J E, Hasselgren P O
Department of Surgery, University of Cincinnati, Ohio 45267-0558, USA.
Shock. 1995 Dec;4(6):403-10.
The influence of sepsis on polyamine metabolism in the liver was studied in rats. Sepsis was induced by cecal ligation and puncture; control rats were sham-operated. Sepsis resulted in increased concentrations in liver tissue of putrescine and spermidine and stimulated activity of the enzymes ornithine decarboxylase (ODC) and s-adenosylmethionine decarboxylase. A similar metabolic response was seen following the subcutaneous injection of 1 mg/kg of endotoxin or following the e intraperitoneal injection of 100 micrograms/kg of human recombinant tumor necrosis factor (TNF)-alpha or interleukin-1 alpha (IL-1 alpha). ODC mRNA levels determined by Northern blots were increased in liver tissue of septic rats, suggesting that the increase in ODC activity may be regulated at the transcriptional level although increased stability of the messenger could give rise to similar results. Treatment of rats with either TNF antiserum, recombinant IL-1 receptor antagonist, or the glucocorticoid receptor antagonist RU 38486, did not prevent the sepsis-induced increase in hepatic ODC activity. The data suggest that sepsis stimulates the biosynthesis of polyamines in liver tissue and that this response to sepsis may not primarily be mediated by TNF, IL-1, or glucocorticoids. The biological role of increased liver polyamines during sepsis, in particular their relationship with the synthesis of acute phase proteins, remains to be determined.
在大鼠中研究了脓毒症对肝脏多胺代谢的影响。通过盲肠结扎和穿刺诱导脓毒症；对照大鼠进行假手术。脓毒症导致肝脏组织中腐胺和亚精胺浓度升高，并刺激鸟氨酸脱羧酶（ODC）和S-腺苷甲硫氨酸脱羧酶的活性。皮下注射1mg/kg内毒素或腹腔注射100μg/kg人重组肿瘤坏死因子（TNF）-α或白细胞介素-1α（IL-1α）后，观察到类似的代谢反应。通过Northern印迹法测定的ODC mRNA水平在脓毒症大鼠的肝脏组织中升高，这表明ODC活性的增加可能在转录水平受到调节，尽管信使RNA稳定性的增加也可能产生类似结果。用TNF抗血清、重组IL-1受体拮抗剂或糖皮质激素受体拮抗剂RU 38486治疗大鼠，不能阻止脓毒症诱导的肝脏ODC活性增加。数据表明，脓毒症刺激肝脏组织中多胺的生物合成，并且这种对脓毒症的反应可能主要不是由TNF,IL-1或糖皮质激素介导的。脓毒症期间肝脏多胺增加的生物学作用，特别是它们与急性期蛋白合成的关系，仍有待确定。
