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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 by which hepatic Kupffer cells (KC) gradually change from defensive to effector during endotoxic liver injury from cellular receptor level. Methods The mouse models of mild, moderate and severe endotoxemia were transplanted via tail vein with different doses of endotoxin (LPS). Intrahepatic KC surface scavenger receptor (SR), CD14 expression was measured by immunohistochemistry, and computer image analysis. Results After 1 h injection of LPS, the expression of SR in KCs at the high dose group was significantly reduced. At 3 h, the expression of SR at KCs began to decrease significantly in both low and medium dose groups. There was a significant difference between the three groups in the absorbance of SR. The expression of CD14 on the surface of KC in the three groups increased significantly 1 h after injection of LPS, and became more obvious with the prolongation of time. However, the absorbance of CD14 in the three groups was not statistically significant. Correlation analysis showed that there was a significant negative correlation between intrahepatic SR and CD14 expression in each dose group. The levels of ALT, TB and MDA in liver tissue were significantly negatively correlated with the down - regulation of SR expression and positively correlated with the up - regulation of CD14 expression. Changes in liver tissue structure and animal mortality also with the intrahepatic KC surface SR, CD14 expression showed a significant parallel. Conclusions Endotoxin-induced liver injury is characterized by down-regulation of SR expression on the surface of KC in the liver and upregulation of CD14 expression, which may be an important mechanism of diminished defense function and increased inflammation.