内毒素血症时肝组织中脂多糖受体CD14的表达及其意义

Expression of lipopolysaccharide receptor CD14 in liver tissue during endotoxemia and its significance

目的 观测内毒素血症时大鼠肝组织中脂多糖受体CD14mRNA的表达及其在内毒素介导Kupffer细胞 (KCs)激活中的作用。方法 经大鼠尾静脉注入内毒素 (剂量按 5mg/kg计算 )建立内毒素血症动物模型 ,测定血浆中内毒素、脂多糖结合蛋白 (LBP)、TNF a及IL 6含量变化 ,同时观测不同时相点肝组织中CD14mRNA的表达及肝组织形态学变化 ,并与生理盐水组大鼠相比较。结果 在内毒素血症组大鼠中 ,随着血浆LPS浓度升高和时间延长 ,肝组织中CD14mRNA的表达明显增强 ;血浆中LBP、TNF a和IL 6含量也明显增加 ,与对照组相比较有显著差异 (P <0 0 1)。伴随KCs激活和肝细胞损伤的形态学改变 ,表现为KCs数量增多、体积增大、噬功能增强 ,肝细胞出现变性、坏死等变化。结论 内毒素血症时 ,随着肝组织中CD14表达增强和血浆LBP增加 ,可介导KCs激活 ,产生和释放多种细胞因子 ,诱导或加重肝组织及其它器官的损害。

Objective To investigate the changes of lipopolysaccharide receptor CD14 in liver tissue and its significance in activation of Kupffer cells (KCs) during endotoxemia. Methods The model of endotoxemia was established by injection of LPS (5 mg/kg, Escherichia coi O111:B4) via the tail vein in Wistar rats. Then the animals were sacrificed at the 1st, 3rd, 6th and 12th hour, respectively. Liver tissue was collected to determine CD14 mRNA expression by RT-PCR. The levels of plasma endotoxin, lopopolysaccharide binding protein (LVP), TNF-a and IL-6 were also determined. The pathological changes of liver tissue were observed with optical and electron microscopy. Results When the level of plasma LPS elevated, expression of CD14 mRNA in the liver tissue was stronger and the level of plasma LBP higher in the experimental group than in the control (P<0.01). KCs were activated. These cells were found to diffusely proliferate and be enlarged in size. Meanwhile, their surface projections were increased in number and their cytoplasm was full of phagocytic vacuoles or electron dense phagosomes, which indicates active phagocytosis. Focal cytoplasmic degeneration and necrosis could be seen in hepatocytes. Conclusions LPS can markedly up-regulate CD14 mRNA expression in liver tissue. KCs are activated by LPS via excessive CD14 gene expression to produce and release various cytokines and may mediate liver and other organ damages.