PROTEIN SYNTHESIS IN LIVER DURING SEPSIS

对脓毒症的代谢反应是不同的，涉及到 蛋白质、碳水化合物、脂肪、微量金属和氨基酸代谢。一个 普遍出现的概念是， 肌肉和肝脏可以用增加的氨基酸流量来概括。 从外周瘦身/肌肉到肝脏的酸类。虽然 脓毒症时肝脏蛋白质合成增加 据报道，其他研究还没有证实这些发现。另外， 肝脏蛋白质合成改变的介体(S)和机制(S) 目前还不完全清楚。建议的目标 研究内容包括：(1)测定肝脏蛋白质合成的变化 脓毒症时在体内和灌流大鼠肝脏中；(2)检测 假设肝脏蛋白质合成增加是由以下因素引起的 白介素1(IL-1)、肿瘤坏死因子(TNF)或其他 单因子；(3)确定分解代谢激素的作用 皮质酮、胰升糖素和肾上腺素治疗加速性肝病 蛋白质合成；以及(4)检验肝脏蛋白质 给药可刺激SPTIC大鼠的合成 不同的底物，其中氨基酸溶液 不同的构图。盲肠结扎诱导大鼠脓毒症 和穿刺法(CLP)；对照动物为假手术。在… CLP或假手术后不同时间点的全肝 蛋白质合成是在体内用水淹剂量测量的。 方法：以14C-亮氨酸为前体氨基酸。在其他 动物产生分泌蛋白质白蛋白， 转铁蛋白、补体成分C3和α1-酸 糖蛋白在灌流的离体肝中使用 放射性标记的循环系统和免疫沉淀 特定的蛋白质。在其他研究中，全肝和分泌性肝 蛋白质合成将在腹腔注射后进行测定 给予活化的大鼠巨噬细胞上清液， 重组IL-1α或重组肿瘤坏死因子。因为它一直是 提示IL-1的一些影响是次要的 糖皮质激素、肝脏蛋白质合成也将被测量 给去肾上腺大鼠注射IL-1。在……里面 另一组实验，分解代谢荷尔蒙将是 在大鼠体内同时输注和肝脏蛋白质合成将 不要吝啬。最后，18-20小时或46-48小时输液的效果 不同组成和新组成的氨基酸溶液在 脓毒症期间肝脏的蛋白质合成将被测定。在 实验相同，对脓毒症大鼠肝脏灌流的影响， 将会被确定。

The metabolic responses to sepsis are varied, involving changes in protein, carbohydrate, fat, trace metal and amino metabolism. A generally emerging concept is that the interaction between muscle and liver may be summarized by increased flow of amino acids from peripherylean body mass/muscle to the liver. Although increased protein synthesis in liver during sepsis has been reported, other studies have not confirmed these findings. Also, mediator(s) and mechanism(s) of altered protein synthesis in liver during spesis are not fully known. The objectives of the proposed studies are to: (1) determine changes in hepatic protein synthesis in vivo and in perfused rat liver during sepsis; (2) test the hypothesis that increased hepatic protein synthesis is induced by interleukin-1 (IL-1), tumor necrosis factor (TNF), or other monokines; (3) determine the role of the catabolic hormones corticosterone, glucagon and epinephrine for accelerated hepatic protein synthesis; and (4) test the hypothesis that hepatic protein synthesis in spetic rats can be stimulated by the administration of different substrates, among them amino acid solutions of different compositions. Sepsis is induced in rats by cecal ligation and puncture (CLP); control animals are sham-operated. At various time-points after CLP or sham-operation, total hepatic protein synthesis is measured in vivo with a flooding dose technique, using 14C-leucine as precusor amino acid. In other animals the production of the secreted proteins albumin, transferrin, complement component C3, and alpha 1-acid glycoprotein is measured in perfused isolated liver using a recirculating system and immunoprecipitation of radiolabeled specific proteins. In still other studies, total and secreted hepatic protein synthesis will be determined following intraperitoneal administration of activated rat macrophage supernatant, recombinant IL-1 alpha or recombinant TNF. Since it has been suggested that some of the effects of IL-1 are secondary to glucocorticoids, hepatic protein synthesis will also be measured following administration of IL-1 to adrenalectomized rats. In another set of experiments, the catabolic hormones will be simultaneously infused in rats and hepatic protein synthesis will be meaured. Finally, the effects of an 18-20 h or 46-48 h infusion of amin acid solutions of various and novel compositions on protein synthesis in liver during sepsis will be determined. In the same of experiments, the effect in perfused liver of septic rats, will be determined.