实验性酒精性肝病时脂多糖结合蛋白和脂多糖受体CD_(14)的表达  

Expression of lipopolysaccharide binding protein and lipopolysaccharide receptor CDl4 in experimental alcoholicliver disease

作　　者：左国庆[1] 何松[1] 刘长安[2] 龚建平[2] 

机构地区：[1]重庆医科大学附属第二医院消化内科,400010 [2]重庆医科大学附属第二医院肝胆外科,400010

出　　处：《中华肝脏病杂志》2002年第3期207-210,共4页Chinese Journal of Hepatology

摘　　要：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。ve To observe the expression of lipopolysaccharide binding protein (LBP) and CD_l4 mRNA inalcohol-induced liver disease (ALD) and evaluate the relationship between the expression of LBP and CD_l4 mRNA and theseverity of liver injury in alcoholic-fed rats, Methods Twenty Wistar rats were divided into two groups: ethanol-fed groupand control group. Ethanol-fed group were fed ethanol (by intragastric infusion of 500 ml/L ethanol orally, dose of 5~12 gkg^(-1)·d^(-l)) and control group received dextrose instead of ethanol. Rats of both groups were sacrificed at 4 weeks and 8 weeks,respectively. Levels of endotoxin and alanine transaminase (ALT) in blood were measured. and liver pathology was ob-served by light and electronic microscopy. Expression of LBP and CD_(l4) mRNA in liver tissues were determined with thereverse transcription polymerase chain reaction (RT-PCR) analysis. Results Plasma endotoxin levels were increased sig-nificantly in ethanol-fed rats [(l29±2l ) pg/ml and (l87±35 ) pg/ml at 4 weeks and 8 weeks] than in control rats [(48±9)pg/ml and (53±ll) pg/ml, respectively, t =ll.2, ll.6, P<0.05]. Mean values for plasma ALT levels were increased dramati-cally in ethanol-fed rats after 4 weeks and 8 weeks [(1l2±l5)U/L and (l47±22)U/L, respectively] than in the controlanimals [(3l±l2)U/L and (33±9)U/L, respectively, t =5.9, 20.6, P<0.05]. In liver sections from ethanol-fed rats, therewas marked pathological changes (steatosis, cell infiltration and necrosis). In the control rats, there was no significant differ-ence in the levels of LBP and CD_(l4) mRNA at the two time points. In ethanol-fed rats, ethanol administration led to a signifi-cant increase in LBP and CD_(l4) InRNA levels as compared with the control group (P<0.05). Conclusions Ethancl adminis-tration lead to a significant increase in endotoxin levels of the serum and LBP and CD_(l4) mRNA expression in liver tissues inethano1-fed rats when compared with the control rats. Increase of LBP and CD_(l4) mRNA expression may result in greatersensiti

关 键 词：酒精性肝病 脂多糖结合蛋白 脂多糖受体 表达 内毒素类 脂多糖受体抗原 CD14 LBP 动物模型 

分 类 号：R575[医药卫生—消化系统]