EFFECT OF SEPSIS ON LIPID METABOLISM

革兰氏阴性脓毒症是创伤患者的主要并发症 损伤、大范围手术、器官移植和严重代谢 疾病 这些拟议的研究将提供一个更好的了解 脓毒症期间脂质代谢紊乱， 临床医生提供更适当的营养支持。 高胆固醇血症和脂肪浸润的肝脏是两个主要的 与革兰氏阴性脓毒症相关的脂质异常。 等离子体 脂蛋白的脂质和载脂蛋白发生改变 混合物. 特别是，高胆固醇血症与 脂蛋白脂酶（LPL）清除机制的缺陷。 此外，脂质在脓毒症大鼠的肝脏中积累， 甘油三酯（TG）、胆固醇和总磷脂的合成 增加了。 喂食结构化脂肪乳剂（SLE），n-3脂肪 酸和中链甘油三酯（MCT），通过连续胃内 输注可防止高脂血症和脂质积聚， 肝脏 待检验的假设为：（1）禁食期间组织LPL的变化 脓毒症状态是由于基因表达的改变， （2）血浆apo B的变化可归因于 肝脏生产率的增加， 载脂蛋白B mRNA水平升高;（3）肝摄取富含TG的 脂蛋白残余颗粒增加，这也有助于 脓毒症脂肪肝;（4）n-3脂肪酸的降脂作用 酸将通过减少载脂蛋白B和TG产生来介导。 脓毒症期间LPL的调节将在禁食和禁食中进行研究。 通过比较LPL活性的变化与测量值， LPL mRNA、LPL合成和LPL质量。 血浆载脂蛋白组成改变的机制 将研究禁食和喂养的脓毒症大鼠中的脂蛋白， 灌注的肝脏，通过确定新生的组成， 脂蛋白、脱辅基蛋白的合成和分泌，以及 肝脏摄取VLDL残余物和LDL。 载脂蛋白B和载脂蛋白 将通过测量载脂蛋白B mRNA和载脂蛋白E mRNA研究E合成。 n-3脂肪酸和MCT的降脂作用机制 将通过测量以下指标进行评价： 血浆脂蛋白、VLDL-TG清除率、 极低密度脂蛋白载脂蛋白B，和合成和分泌的脂质和载脂蛋白， 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.