凉膈散对内毒素血症小鼠的肝脏库普弗细胞CD14和清道夫受体表达的影响

Liangge San effects the expression of CD14 and scaverger receptor in the kupffer cells of liver of endotoxemia mice

目的:探讨凉膈散对内毒素血症小鼠的肝脏库普弗细胞CD14和清道夫受体(SR)的表达的影响以及肝脏(LPS)引起损伤的影响,从细胞信号转导途径阐明中药解毒机制。方法:建立内毒素血症小鼠动物模型,同时灌服凉膈散,在内毒素给药后不同时间点(2,4,8 h)杀动物取肝组织,免疫组化法观察肝脏库普弗细胞CD14及SR表达的变化,并进行图像分析和肝组织的病理检测。结果:注射LPS 2,4,8 h后,与正常对照组相比,LPS损伤组肝脏库普弗细胞CD14的表达均呈显著升高,SR表达均呈显著降低(P<0.01)。不同剂量凉膈散组及地塞米松组均介于正常对照组与LPS损伤组之间。与LPS损伤组比较,不同剂量凉膈散组及地塞米松组在两者的表达上均有显著性差异(P<0.01),以高剂量凉膈散最为明显,呈剂量相关性。肝脏损伤主要表现为空泡变性,肝脏库普弗细胞SR,CD14的表达变化与小鼠肝损伤程度呈平行关系。结论:凉膈散对内毒素血症小鼠的肝脏库普弗细胞表面CD14表达上调以及SR表达下调有明显的抑制作用,并能减轻内毒素所致的肝损伤。

Objective： To study the effects of Liangge San to the expression of CD14 and scaverger receptor（SR） in the kupffer cells of liver and the pathological changes of liver tissue of endotoxemia-mice. Method： The model was established with intravenous injection of lipopolysaccharide（LPS） and at the same time different dose Liangge San were given. The expression of CD14 and scaverger receptor were detected with immunohigtochemistry at the 2^nd, 4^th, 8^th hour offer injury and analyzed with computer image system, and the pathological changes of liver tissue were also observed. Result： At the three different hours, the expression of CD14 and scaverger receptor in macrophages of liver of LPS-injury group showed significant increase and significant decrease respectively, compared with that of the blank-control group （ P 〈 0.01）. The expression in dexamethasone group and Liangge San different dose groups were intermediate between those in injury group and those in control group. Compared with expression of LPS-injury group, those of dexamethasone group and Liangge San different dose groups showed significant differences（ P 〈 0.01 ）, especially that of Liangge San high dose group. Liver cells showed vacuole change. Changes of CD14 and SR expression were paralleled with the severity of liver damages of the mice. Concluion： Liangge San can inhibite the up-regulation of CD14 expression and down-regulation of scaverger receptor expression in a dosage-dependent manner and also alleviate the damages of liver induced by LPS.