内毒素血症时血浆氧化型低密度脂蛋白的变化及其对库普弗细胞-内毒素反应的影响  

Changes of plasma oxidized low-density lipoprotein levels during endotoxemia and its effect on Kupffer's cell response to LPS

作　　者：吉善和[1] 蒋建新[2] 张宇[2] 单佑安[2] 刘大维[2] 朱佩芳[2] 

机构地区：[1]新疆呼图壁解放军第十五医院骨科,831200 [2]第三军医大学附属大坪医院野战外科研究所第四研究室,重庆400042

出　　处：《中华创伤杂志》2002年第2期108-110,共3页Chinese Journal of Trauma

基　　金：国家重点基础研究发展规划基金资助项目(G19990 5 42 0 0 ) ;国家自然科学基金资助项目 ( 39770 313;39870 833) ;军队杰出中青年基金资助项目

摘　　要：目的　探讨内毒素血症时血浆氧化型低密度脂蛋白 (Ox -LDL)的变化规律及Ox -LDL对库普弗细胞 (KC) -内毒素 (LPS)反应的影响。　方法　Wistar大鼠 3 6只 ,随机分为对照组( 6只 )和LPS组 (分为 1,5 ,10mg kg三组 ,每组 10只 ) ,复制大鼠内毒素血症模型 ,采用ELISA方法检测对照组及注射内毒素后 0 .5 ,1,3 ,5 ,8h时血浆Ox -LDL水平变化及其与LPS的量效关系。分离培养小鼠KC ,分别用Ox-LDL( 10～ 10 0 μg ml)、抗小鼠清道夫受体 (SR)单抗 ( 10 μg ml)及抗CD14单抗 ( 10 μg ml) +Ox -LDL( 10 0 μg ml)预处理KC 1h后 ,再分别与 1,10ng mlLPS孵育 3h ,观察以上预处理对LPS诱导KC释放肿瘤坏死因子 -α(TNF -α)的影响及其与KC表面CD14的关系。细胞上清TNF -α水平采用ELISA法检测。　结果　注射LPS后 ,3组大鼠血浆Ox -LDL水平均显著增高 ,以 10mg kg组升高最明显。Ox -LDL预处理KC ,能显著增强内毒素对KC的激活作用 ,表现为TNF -α含量明显升高 ,呈明显的量效关系。Ox -LDL的这种增强作用与抗SR抗体影响LPS刺激KC的作用相同 ,而抗CD14抗体可完全抑制Ox-LDL的这种增强作用。　结论　内毒素血症早期血浆Ox-LDL水平明显增高 ,与LPS呈明显的量效关系 ;Ox -LDL能明显增强LPS对KC的激活作用 。Objective To investigate the kinetics of plasma oxidized low density lipoprotein levels (Ox LDL) in endotoxemia, and the effect of Ox LDL on Kupffer cell(KC) response to lipopolysaccharide (LPS) stimulation. Methods Intravenous injection of 1, 5 or 10 mg/kg LPS induced rat models of endotoxemia. Plasma Ox LDL level was assayed by using ELISA kit. KCs isolated from mice were cultured and then pretreated with Ox LDL(10 - 100 μg/ml) or anti SR mAb(10 μg/ml) or anti CD14 mAb ( 10 μg/ml ) plus Ox LDL(100 μg/ml) for 1 h before LPS stimulation. Supernatants were collected 3 hours after LPS challenge for TNF α assay. Results Plasma Ox LDL levels increased significantly in all of the three groups after injection of LPS, in which the 10 mg/kg group increased most significantly. Pretreatment of KC with Ox LDL could markedly enhance the LPS induced activation of KCs, as shown by increased levels of TNF α in supernatants. This enhancement of Ox LDL was in dose dependent manner, and similar to the effect of anti SR mAb on KC response to LPS. Anti CD14 mAb could completely inhibit LPS induced activation of KCs. Conclusions This experiment indicates that plasma Ox LDL levels can significantly increase at the early stage of endotoxemia in a dose dependent manner. Ox LDL can significantly enhance LPS induced activation of KCs, which may be related to promotion of LPS binding to CD14 on the surface of KCs by Ox LDL.

关 键 词：内毒素血症 脂蛋白类 LDL 库普弗细胞 抗原 CD14 清道夫受体 

分 类 号：R459.7[医药卫生—急诊医学]