内毒素血症小鼠血浆Ox-LDL的变化及其对LPS致炎效应的影响

Changes of plasma oxidized low-density lipoprotein in endotoxemia mice and effects on the inflammatory ability of LPS

目的 探讨内毒素血症小鼠血浆氧化型低密度脂蛋白(Ox LDL)的变化规律及其对内毒素(LPS)作用的影响。方法 静脉分别注射LPS 1、2 5、5mg kg ,复制小鼠内毒素血症模型,ELISA法检测血浆Ox LDL含量;Ox LDL 0 3 5、1 4mg kg静脉注射预处理小鼠,3 0min后注射LPS 1mg kg ,ELISA法测定血浆TNF α含量;观察Ox LDL预处理对内毒素血症小鼠2 4h死亡率的影响。结果 内毒素血症小鼠血浆Ox LDL明显升高,LPS注射后0 5～8h ,各剂量组血浆Ox LDL水平均显著高于正常对照(P <0 0 1) ;不同剂量Ox LDL预处理小鼠血浆TNF α水平均显著高于LPS单纯注射组同时相点(P <0 0 1) ,且2 4h死亡率增加。结论 内毒素血症小鼠血浆Ox LDL水平明显增高,与LPS呈明显的量效关系;Ox LDL能增强LPS的致炎效应,这可能与其部分封闭清道夫受体(SR) ,导致LPS清除减少有关。

Objective To investigate the changes of plasma oxidized low-density lipoprotein (Ox-LDL) in endotoxemia mice and its effects on the inflammatory ability of lipopolysaccharide (LPS). Methods Endotoxemia model of 120 mice was duplicated with 1, 2.5 and 5 mg/kg of LPS intravenous injection respectively, and plasma Ox-LDL levels were assayed using ELISA kit at 0.5, 1, 2, 4, 8 h after LPS injection, and another 8 mice without any treatment served as normal control. Another 105 mice were divided into 3 groups pretreated with 0, 0.35 and 1.4 mg/kg of Ox-LDL intravenous injection 30 min before 1 mg/kg of LPS intravenous injection. Plasma TNF-α levels were measured with ELISA at 0, 1, 2, 4, 8 h after the first injection. The effects of Ox-LDL pretreatment on the mortality of another 150 endotoxemia mice 24 h after LPS injection was observed, which were treated with the same methods as 105 mice. Results Plasma Ox-LDL levels in endotoxemia mice increased significantly. In 0.5 to 8 h after LPS injection, plasma Ox-LDL levels were significantly higher than that of control group (P<0.01). Plasma TNF-α levels in all the Ox-LDL pretreated groups were remarkably higher than that of the only LPS injected group at the same time point (P<0.01), and the mortality of mice pretreated with Ox-LDL at 24 h after LPS injection increased. Conclusion Plasma Ox-LDL levels of endotoxemia mice increased significantly in a dose-dependent manner. Ox-LDL could remarkably enhance the inflammatory ability of LPS, which may due to blockage of scavenger receptors by Ox-LDL.