肝星形细胞CD14表达变化在内毒素肝损伤中的作用

Dynamic Expression of CD14 on Kupffer Cells in Endotoxin-induced Hepatic Injury

目的 观察内毒素肝损伤过程中肝星形细胞 (枯否细胞 ,KC) CD14表达及肿瘤坏死因子、白细胞介素 - 6的动态变化 ,进而探讨内毒素肝损伤的机理。方法 经尾静脉内注射不同剂量 (1mg/ kg、10 mg/ kg)大肠埃希菌内毒素 (L PS) ,复制内毒素肝损伤模型 ;采用免疫组化方法观察小鼠肝脏 CD14表达变化 ;酶联免疫吸附法 (EL ISA)测定肝组织 TNFα、IL - 6的水平 ,光镜观察肝组织学变化。结果 内毒素肝损伤过程中 ,KC表面 CD14表达呈进行性上调 ,且与内毒素呈明显的量效关系 ;CD14表达的平均光密度值 (OD值 )与肝组织 TNFα、IL - 6及血浆丙氨酸氨基转移酶 (AL T)、总胆红素 (TBIL )呈显著的正相关。结论 内毒素肝损伤过程中 ,随着 CD14表达上调 ,内毒素对库普弗细胞的激活作用则相应增强 ,释放促炎因子 TNFα、IL - 6等进一步增加 ,加重肝组织的损伤 ;肝星形细胞 CD14表达上调可能是内毒素肝损伤的重要机理之一。

OBJECTIVE To observe the changes in CD14 expression on Kupffer cells(KC) and the kinetics of inflammatory mediators TNFα,IL 6 levels in hepatic tissue, and to investigate the mechanism of hepatic injury.METHODS After 1 mg/kg or 10 mg/kg of E.coli 026∶B6 LPS in form of endotoxin was injected via to caudal vein to reproduce an animal model for this experiment. The changes in CD14 expression on KC were determined with immunohistochemistry. TNFα, IL 6 levels in hepatic tissue were assayed using ELISA. RESULTS The expression of CD14 was gradually up regulated, which was not significantly among small, moderate and large dose groups. TNFα and IL 6 levels in hepatic tissue and ALT, TBIL in plasma were significant positive with the expression of CD14.CONCLUSIONS The changes in CD14 expression on KC might be closely related with hepatic injury, namely,with the expression of CD14 up regulated. The activation of KC by endotoxin was accordingly enhanced. It was found that the concentrations of TNFα and IL 6 successively and significantly increased,leading to more severe hepatic injury. The expression of CD14 up regulated might be a part of the mechanism of hepatic injury.