腺苷酸激活蛋白激酶在大鼠酒精性肝病中的表达减少

AMPK expression decreases in alcoholic liver disease

目的观察酒精对大鼠肝脏腺苷酸激活化蛋白激酶(AMPK)表达水平的影响及意义。方法雄性Wistar大鼠50只,随机分为模型组和对照组,模型组采用乙醇灌胃法,分别于4、8、12和16周末随机分批处死,检测其血清ALT、AST、CHE、TG、TC、LDL、VLD和HDL;应用HE、天狼红及苏丹Ⅳ染色观察肝组织病理变化;应用免疫组织化学染色、RT-PCR法检测AMPK、乙酰辅酶A羧化酶(ACC)和固醇调节原件结合蛋白(SREBP)及其mRNA的表达。结果随着造模时间延长,大鼠血清ALT、AST、TG、TC和LDL水平逐渐升高,CHE和HDL水平逐渐降低;模型16周组肝组织中AMPK的表达为0.50±0.094,显著低于对照组的0.84±0.041,而ACC及SREBP表达逐渐多于对照组(P<0.05);肝组织AMPK与ACC及SREBP的表达呈负相关(P<0.01)。结论酒精性肝病中AMPK表达减少,导致脂质合成增多,脂肪堆积于肝脏中,可能是造成肝脏损伤的重要因素。

Objective To observe the effects of ethanol consumption on the expression of AMP-activated protein kinase（AMPK） in the rats hepatic tissue with alcoholic liver disease（ALD）.Methods In the 50 male Wistar rats,10 rats were randomly assigned to the control group.Others were to develop the rats model of ALD by intragastric alcohol and sacrificed randomly at the end of 4th,8th,12th and 16th week,and the serum and liver samples were collected respectively.The contents of ALT,AST,CHE,TG,TC,LDL,VLDL and HDL in serum were examined and the pathological changes were observe in liver tissue by HE,Sirius red.and Sudan Ⅳ.The protein expression of AMPK,Acetyl-CoA carboxylase（ACC）,Sterol regulatory element-binding proteins（SREBP） and mRNA were detected by immunohisto-chemical staining and RT-PCR respectively.Results With the consumption of ethanol,the level of ALT and AST in the serum increased while the CHE decreased gradually.The level of TG,TC,LDL and VLDL in the serum increased while the HDL decreased gradually.Compared with the control group,the expression of AMPK in model group decreased gradually with the progress of ALD,and it negatively correlated with the expression of ACC and SREBP of hepatic tissue（r=-0.911 and-0.907 respectively,P0.01）.Conclusions The expression of AMPK in hepatic tissue is decreased with the process of ALD,which inhibits the activation to ACC and SREBP.It causes the increase of lipid synthesis,which may result in the fat accumulation in the liver and has a great effect on the liver injury.