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目的 观察大鼠酒精性肝病时脂多糖结台蛋白(lipopolysaccharide binding protein,LBP)和脂多糖受体CD_(14)的表达及其在酒精性肝损害中的作用。方法 随机将Wistar大鼠分为乙醇喂养组和葡萄糖喂养对照组,分别在饮水中加入乙醇(剂量5~12g·kg~(-l)·d~(-1))和相同量的葡萄糖。两组大鼠分别于4周和8周测定其血浆中内毒素(LPS)浓度及血清中ALT变化,同时用RT-PCR测定肝组织中LBP和CD_(14) mRNA的表达,并在光镜和电镜下观察肝脏的形态学改变。结果 乙醇喂养组4周和8周时大鼠血浆LPS浓度分别为(129±21)pg/ml和(187±35)pg/ml,明显高于对照组的(48±9)pg/ml和(53±11)pg/ml(t值分别为11.2和11.6. P＜0.05); 乙醇组大鼠血清ALT浓度为(112±15)U/L 和(147±22)U/L,也明显高于对照组的(31±12)U/L和(33±9)U/L(t值分别为5.9和20.6. P＜0.05)。乙醇组大鼠肝组织中LBP和CD_(14) mRNA的表达水平明显高于对照组(P＜0.05),其肝组织发生显著的病理变化,主要表现为脂肪变性、炎性细胞浸润及细胞坏死。对照组肝组织中LBP和CD_(14) mRNA无明显表达,其病理变化也不明显。结论 乙醇能诱导大鼠血中LPS浓度升高和肝组织中LBP与CD_(14) mRNA的表达显著增强、增高的LBP和CD_(14) mRNA能增加肝脏对LPS的敏感性,可能造成肝脏损害。
Objective To investigate the expression of lipopolysaccharide binding protein (LBP) and lipopolysaccharide receptor CD_ (14) in alcoholic liver disease and its role in alcoholic liver injury. Methods Wistar rats were randomly divided into ethanol-fed group and glucose-fed control group. Ethanol (5-12 g · kg -1 · d -1) and the same amount of glucose were added to drinking water respectively. The levels of plasma endotoxin (LPS) and serum ALT in the two groups were measured at 4 and 8 weeks respectively. The expression of LBP and CD_ (14) mRNA in liver tissue was detected by RT-PCR. The morphological changes of the liver were observed under electron microscope. Results Plasma concentrations of LPS were (129 ± 21) pg / ml and (187 ± 35) pg / ml at 4 weeks and 8 weeks in ethanol-fed group, which were significantly higher than those in control group (48 ± 9) pg / ml and (53 ± 11) pg / ml (t = 11.2 and 11.6, P <0.05, respectively). Serum ALT concentrations in ethanol group were (112 ± 15) U / L and (147 ± 22) U / L, (31 ± 12) U / L and (33 ± 9) U / L higher than the control group (t = 5.9 and 20.6, P <0.05). The expression of LBP and CD_ (14) mRNA in the liver of ethanol group was significantly higher than that of the control group (P <0.05), and the pathological changes of liver tissue were observed. The main changes were steatosis, inflammatory cell infiltration and necrosis . The control group had no obvious expression of LBP and CD_ (14) mRNA, and the pathological changes were not obvious. Conclusion Ethanol can induce the increase of LPS concentration in rat blood and the expression of LBP and CD_ (14) mRNA in liver tissue. The increased LBP and CD_ (14) mRNA can increase the liver sensitivity to LPS and may cause liver damage .