SEPSIS EFFECT ON LIPID METABOLISM

革兰氏阴性败血症是创伤患者的主要并发症。 受伤，大手术，器官移植和严重的代谢 疾病。这些拟议的研究将提供更多的了解 脓毒症期间脂代谢的紊乱，从而使 为临床医生提供更合适的营养支持。 高甘油三酯血症和肝脏脂肪浸润症是两个主要的 与革兰氏阴性脓毒症相关的脂质异常。血浆 脂蛋白的脂类和载脂蛋白会发生改变 组成。特别是，高甘油三酯血症与 脂蛋白脂酶(LPL)清除机制的缺陷。 此外，脓毒症大鼠的肝脏中脂质积聚是因为 甘油三酯、胆固醇和总磷脂的合成 都增加了。喂养结构化脂肪乳剂(SLE)，n-3脂肪 酸和中链甘油三酯(MCT)，连续灌胃 输液预防高甘油三酯血症和脂肪堆积 肝脏。 需要检验的假设是：(1)禁食期间组织LPL的变化 败血症状态是由于基因表达的变化引起的 (2)血浆载脂蛋白B的变化可归因于 肝脏生成率的增加，这与 高水平的载脂蛋白B mRNA，(3)肝脏摄取富含甘油三酯 脂蛋白残存颗粒增加，这也是导致 脓毒症脂肪肝；(4)n-3脂肪的降脂作用 酸将通过减少载脂蛋白B和甘油三酯的产生来调节。 脓毒症时LPL的调节将在空腹和 通过比较LPL活性的变化和测量结果来喂养脓毒症大鼠 LPL信使核糖核酸、LPL合成和LPL质量。 血浆载脂蛋白组成改变的机制 禁食和喂养脓毒症大鼠的脂蛋白将在完整的 通过测定新生肝脏的成分来灌流肝脏 脂蛋白，载脂蛋白的合成和分泌，以及 肝脏摄取极低密度脂蛋白残留物和低密度脂蛋白。载脂蛋白B和载脂蛋白B的调节 通过测定载脂蛋白B和载脂蛋白E的mRNA来研究E的合成。 N-3脂肪酸和MCT的降脂作用机制 将通过测量：脂类和载脂蛋白的组成进行评估 血浆脂蛋白、极低密度脂蛋白-甘油三酯清除率、低密度脂蛋白摄取 极低密度脂蛋白载脂蛋白B与脂类和载脂蛋白的合成与分泌 原代培养肝细胞。

Gram-negative sepsis is a major complication for the patient with trauma injuries, extensive surgery, organ transplant, and severe metabolic diseases. These proposed studies will provide a greater understanding of the disturbances in lipid metabolism during sepsis thus enabling clinicians to provide more appropriate nutritional support. Hypertriglyceridemia and fatty infiltration of the liver are two major lipid abnormalities associated with gram-negative sepsis. The plasma lipoproteins are altered with respect to their lipid and apoprotein composition. In particular, the hypertriglyceridemia is associated with a defect in the lipoprotein lipase (LPL) clearing mechanism. Additionally, lipids accumulate in the livers of the septic rats because the synthesis of triglycerides (TG), cholesterol, and total phospholipids are increased. Feeding a structured lipid emulsion (SLE), n-3 fatty acids and medium chain triglycerides (MCT), by continuous intragastric infusion prevents hypertriglyceridemia and lipid accumulation in the liver. The hypotheses to be tested are: (1) changes in tissue LPL during fasted septic state are due to alterations in the genetic expression which are modified by feeding, (2) the changes in plasma apo B can be attributed to an increase in the rates of liver production which is associated with higher levels of apo B mRNA, (3) the hepatic uptake of TG-rich lipoprotein remnant particles is increased which also contributes to the fatty liver of sepsis, and (4) the lipid-lowering effects of n-3 fatty acids will be mediated by decreasing apo B and TG production. The regulation of LPL during sepsis will be investigated in fasted and fed septic rats by comparing changes in LPL activity with measurements of LPL mRNA, synthesis of LPL, and LPL mass. The mechanism for the altered apoprotein composition of the plasma lipoproteins in fasted and fed septic rats will be studied in the intact perfused liver by determining the composition of the nascent lipoproteins, the synthesis and secretion of the apoproteins, and the liver uptake of VLDL remnants and LDL. The regulation of apo B and apo E synthesis will be studied by measuring apo B mRNA and apo E mRNA. The mechanism for the lipid-lowering effects of n-3 fatty acids and MCT will be evaluated by measuring: the lipid and apoprotein composition of the plasma lipoproteins, the clearance rates of VLDL-TG, the uptake of VLDL apo B, and synthesis and secretion of lipids and apoproteins in primary cultured hepatocytes.