库普弗细胞清道夫受体、CD14表达变化及其与内毒素性肝损伤的关系  

Expression of scavenger receptor and CD14 on Kupffer cells and its relationship with endotoxin-induced hepatic injury

作　　者：蒋建新[1] 谢国旗[1] 陈永华[1] 刘大为[1] 周继红[1] 朱佩芳[1] 王正国[1] 张洪杰[1] 

机构地区：[1]第三军医大学附属大坪医院野战外科研究所,重庆400042

出　　处：《中华创伤杂志》2000年第8期478-481,共4页Chinese Journal of Trauma

基　　金：国家重点基础研究发展规划项目!(G19990 5 42 0 0);国家自然科学基金!资助项目 (No.39770 313);军队杰出中青年科学基金

摘　　要：目的　从细胞受体水平探讨内毒素性肝损伤过程中肝内库普弗细胞 (KC)由防御性逐步转化为效应性的机制。　方法　经尾静脉注射不同剂量内毒素 (LPS)复制轻、中、重度内毒素血症小鼠模型。肝内KC表面清道夫受体 (SR)、CD14表达测定采用免疫组化法 ,并进行计算机图像分析。　结果　注射LPS后 1h ,高剂量组肝内KC表面SR表达明显减少 ,至 3h ,低剂量和中剂量组KC表面SR表达也开始明显减少 ,并随观察时间延长 ,3组KC表面SR表达均进行性减少 ,3组间SR的吸光度差异有显著性意义。 3组肝内KC表面CD14表达在注射LPS后 1h均明显增多 ,并随时间延长而更加明显 ,但 3组间CD14的吸光度无统计学意义。相关分析显示 ,各剂量组肝内SR与CD14表达变化呈显著负相关。血浆丙氨酸氨基转移酶 (ALT)、总胆红素 (TB)和肝组织内丙二醛 (MDA)水平变化分别与SR表达下调呈显著负相关 ,与CD14表达上调呈显著正相关。肝组织结构改变及动物死亡率也与肝内KC表面SR、CD14表达变化呈明显的平行关系。　结论　内毒素致肝损伤过程中 ,肝内KC表面SR表达下调、CD14表达上调可能是KC防御功能减弱、致炎作用增强的重要机制。Objective To investigate the mechanism for Kupffer cells (KC) to be converted into effector cells from defense cells at the level of cell receptor in endotoxin-induced hepatic injury. Methods Mouse model of endotoxemia of different severity was produced by injection of different doses of lipopolysaccharide (LPS) via tail vein. The expression of scavenger receptor (SR) and CD14 on KC surface was assayed by immunohistochemistry and then analyzed with computer imaging system. Results The expression of SR on KC in the high-dose group was markedly decreased 1 hour after injection of LPS, and also in the low- and medium-dose groups 3 hours after injection, which in the three groups was shown to be aggressively decreased with the time prolonged. There was significant difference in obtained absorb (OD) values of SR among the three groups. The expression of CD14 on KC in the three groups was shown to be significantly increased 1 hour after injection of LPS, and much more significantly with the time prolonged. But there was no significant difference in OD values of CD14 among the three groups. Correlation analysis showed that there was negative correlation between expression of SR and CD14. The changes of alanine aminotransferase and total bilirubin levels in plasma and malondialdehyde content in liver tissue were correlated negatively with SR down-regulation and positively with CD14 up-regulation, respectively. The hepatic morphologic alteration and animal mortality rate were also shown to be paralleled with the expression of SR and CD14 on KC. Conclusions The down-regulation of SR and up-regulation of CD14 on KC might be the important mechanism for decreased defense function and increased pro-inflammatory response of KC during endotoxin-induced hepatic injury.

关 键 词：库普费细胞 CD14 抗原 内毒素血症 清道夫受体 

分 类 号：R363[医药卫生—病理学]