库普弗细胞SR表达变化与内毒素肝损伤的关系

Relationship between the dynamic expression of scavenger receptor on Kupffer cells and endotoxin-induced hepatic injury

目的 观察内毒素肝损伤过程中库普弗细胞（ＫＣ）清道夫受体（ＳＲ）表达的动态变化，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．１０ｍｇ／ｋｇ）大肠杆菌内毒素（ＬＰＳ），复制内毒素肝损伤模型。采用免疫组织化学方法观察小鼠肝脏ＳＲ表达变化；酶联免疫吸附法（ＥＬＩＳＡ）测定肝组织 ＴＮＦＦ α、ＩＬ－６的水平，光镜观察肝组织学变化。结果（１）内毒素肝损伤过程中，ＫＣ表面ＳＲ表达呈进行性下调，且与内毒素呈明显的量效关系。（２）ＳＲ表达的平均光密度值（Ａ值）与肝组织 ＴＮＦ α、ＩＬ－６及血清ＡＬＴ、ＴＢｉｌ呈显著的负相关。结论 内毒素肝损伤过程中，随着ＳＲ表达下调，ＫＣ对内毒素的清除作用下降，内毒素对ＫＣ的激活作用则相应增强。ＫＣ ＳＲ表达变化与肝损伤密切相关。

Objective: To observe the change of scavenger receptor (SR) expression on Kupffer cells and study its role in pathogenesis of liver injury in mice. Methods 1mg/kg or 10 mg/kg of E.Coli 026: B6 LPS was bolus injected via i. a.to reproduce an animal model for this experiment. The change of SR on Kupffer cells was determined with immunohistochemistry. TNF-α and IL-6 level in hepatic tissue were assayed using ELISA. Results The expression of SR on Kupffer cells was aggressively downregulated in a LPS does dependent fashion. TNF- α, IL-6 level in hepatic tissue and ALT, TBIL in plasma were significantly negatively correlated with the expression of SR. Conclusions With the downregulation of SR expression on Kupffer cells, the clearance of endotoxin by Kupffer cells is decreased and the activation of Kupffer cells by endotoxin is accordingly enhanced. SR expression is closely related to hepatic injury.