EFFECT OF SEPSIS ON LIPID METABOLISM

这个实验室之前的发现表明， 与革兰氏阴性败血症相关的高甘油三酯血症是一种 甘油三酯清除率降低的后果 血。尽管肝脏甘油三酯、胆固醇和 在革兰氏阴性脓毒症期间磷脂含量较高，分泌的 甘油三酯受损，导致肝脏积聚。 这项研究将进一步确定可能导致变化的因素 极低密度脂蛋白甘油三酯的清除 根据其大小和大小来表征血浆脂蛋白 载脂蛋白和脂类组成，决定B的去除率 通过肝脏的载脂蛋白，并测量肝脏摄取极低密度脂蛋白 残留物。 肝脏甘油三酯分泌减少的机制将是 用原代培养的肝细胞测定合成能力进行评价 以及分离的脂蛋白的载脂蛋白和脂类的分泌。 载脂蛋白合成的调节将通过测量 对葡萄糖、脂肪酸和激素(胰岛素、胰高血糖素和 地塞米松)对载脂蛋白合成和分泌的影响 还有血脂。 研究肝脏甘油三酯合成增加的原因 革兰氏阴性脓毒症，原代培养的肝细胞将用于 测量脂肪酸的摄取量，甘油的浓度 磷酸盐和丙二酸辅酶A，以及磷脂酸酯的活性 磷酸水解酶、甘油磷酸酰基转移酶和肉碱 棕榈酰基转移酶。 这些关于脂蛋白新陈代谢的拟议研究是 有必要加深我们对 革兰氏阴性败血症时高甘油三酯血症的发生。 从这些实验中获得的信息将为 更好的营养支持。

Previous finding from this laboratory indicate that the hypertriglyceridemia associated with gram-negative sepsis is a consequence of a decrease in the rate of triglyceride clearance from the blood. Although synthesis rates of liver triglycerides, cholesterol, and phospholipids are higher during gram-negative sepsis, the secretion of triglycerides is impaired resulting in an accumulation in the liver. This study will define further the factors that may lead to changes in the clearance of very-low-density lipoprotein (VLDL) triglycerides by characterizing the plasma lipoproteins with respect to their size and apoprotein and lipid composition, determining the removal rate of the B apoproteins by the liver, and measuring the liver uptake of VLDL remnants. The mechanism for the reduced secretion of liver triglycerides will be evaluated by using primary cultured hepatocytes to measure the synthesis and secretion of the apoproteins and lipids of the isolated lipoproteins. The regulation of apoprotein synthesis will be studied by measuring the effect o glucose, fatty acids, and hormones (insulin, glucagon, and dexamethasone) on the rates of synthesis and secretion of the apoproteins and lipids. To study why triglyceride synthesis is increased in the liver during gram-negative sepsis, primary cultured hepatocytes will be used to measure the uptake of fatty acids, the concentration of glycerol 3 phosphate and malonyl coenzyme A, and the activities of phosphatidate phosphohydrolase, glycerophosphate acyltransferase and carnitine palmitoyltransferase. These proposed studies on the metabolism of the lipoproteins are necessary to further our understanding of the mechanisms involved in the development of hypertriglyceridemia during gram-negative sepsis. Information obtained from these experiments will provide guidelines for better nutritional support.