EFFECT OF SEPSIS ON LIPID METABOLISM

脓毒症引起的碳水化合物和蛋白质代谢的改变是 详细描述，但在脂质代谢异常是差 明白 脓毒症时高胆红素血症的发生机制 仍然未知。 这可能是由于甘油三酯的产生增加 脂蛋白脂酶的外周清除减少，和/或 肝脏分泌速率增加。 本研究将确定并描述导致 革兰氏阴性脓毒症期间脂质代谢改变。 血脂的变化 代谢将通过测量体内血清脂质、合成 肝脏和脂肪组织中脂质类的比率， 脂蛋白脂酶，肝脂肪生成酶，甘油三酯 脓毒症大鼠的分泌和清除以及胰岛素和胰高血糖素水平 模型 肝脏的作用将通过确定 新鲜分离的肝细胞中脂质类的体外合成 禁食脓毒症大鼠和禁食对照大鼠。 来区分食物的影响 限制和败血症对脂质代谢的影响，脂质合成将 在来自胃内喂养大鼠的分离肝细胞中测量。 的 在分离的肝细胞中观察到的脂质合成异常将 通过使用分离的原代培养物进一步研究 肝细胞 这些原代培养物的实验将确定 脂质合成的恢复时间，不同底物的影响， 存在或不存在胰岛素对脂质合成的影响，以及 细胞外因子通过进行交叉研究。 肝细胞 将正常和脓毒症大鼠与脓毒症大鼠血清和正常血清一起孵育。 这些研究将阐明高胆固醇血症的机制， 脓毒症，并希望作为基础，开发更好的营养 为脓毒症患者提供支持。

The sepsis-induced alterations in carbohydrate and protein metabolism are described in detail, yet the abnormalities in lipid metabolism are poorly understood. The mechanism causing hypertriglyceridemia during sepsis remains unknown. This could result from increased triglyceride production by the liver, reduced peripheral removal by lipoprotein lipase, and/or an increase in liver secretion rate. This study will identify and describe the mechanism(s) responsible for the altered lipid metabolism during gram-negative sepsis. The changes in lipid metabolism will be assessed by measuring in vivo serum lipids, synthesis rates of the lipid classes in liver and adipose tissue, activities of lipoprotein lipase, the liver lipogenic enzymes, rates of triglyceride secretion and clearance, and insulin and glucagon levels in a septic rat model. The role of the liver will be evaluated further by determining in vitro synthesis of the lipid classes in freshly isolated hepatocytes from fasted septic and fasted control rats. To distinguish the effects of food restriction and sepsis on lipid metabolism, lipid synthesis will be measured in isolated hepatocytes from intragastrically-fed rats. The observed abnormalities of lipid synthesis in the isolated hepatocytes will be investigated further by using primary cultures of the isolated hepatocytes. These experiments with the primary culture will define the recovery time of lipid synthesis, the effect of different substrates in the presence or absence of insulin on lipid synthesis, and the presence of extracellular factor(s) by performing cross-over studies. Hepatocytes from normal and septic rats are incubated with septic rat serum and normal serum. The proposed studies will clarify the mechanism of hypertriglyceridemia in sepsis and hopefully serve as a basis for developing better nutritional support for the septic patient.