腺苷酸激活蛋白激酶在大鼠酒精性肝病中的表达减少

基础医学与临床 ›› 2012, Vol. 32 ›› Issue (10): 1154-1160.

腺苷酸激活蛋白激酶在大鼠酒精性肝病中的表达减少

周东方¹,魏峰²,周俊英²

1. 河北医科大学第三医院
2. 河北医科大学第三医院感染科

收稿日期:2011-09-20 修回日期:2012-01-05 出版日期:2012-10-05 发布日期:2012-09-28
通讯作者: 周俊英 E-mail:doctorzhoujy@163.com
基金资助:
河北省卫生厅科技攻关项目

AMPK expression decreases in alcoholic liver disease

Received:2011-09-20 Revised:2012-01-05 Online:2012-10-05 Published:2012-09-28

摘要/Abstract

摘要： 【摘要】：目的：观察酒精对大鼠肝脏腺苷酸活化蛋白激酶（AMPK）表达水平的影响。方法：雄性Wistar大鼠50只，随机分出10只为正常对照组，其余动物采用酒精灌胃的方法，随机分为模型4、8、12、16周组，留取血清及肝组织标本；检测血清ALT、AST、CHE、TG、TC、LDL、VLD、HDL等生化指标，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、ACC、SREBP蛋白及mRNA的表达。结果：随着酒精造模时间延长，血清ALT和AST水平逐渐升高，CHE水平逐渐降低；血清TG、TC、LDL水平逐渐升高，HDL水平逐渐降低；肝组织中AMPK表达逐渐减少，ACC及SREBP表达逐渐增多；肝组织AMPK与ACC及SREBP的表达呈负相关(r=-0.911, P<0.01; r=-0.907, P<0.01)。结论：ALD发病过程中AMPK表达减少，对ACC、SREBP活化的抑制作用减弱，脂质合成增多，造成脂肪堆积于肝脏中，是造成肝脏损伤的重要因素。AMPK作为一个新的药物靶点，为ALD的防治提供了新的思路。

关键词: 腺苷酸活化蛋白激酶, 酒精性肝病, 乙酰辅酶A羧化酶, 固醇调节元件结合蛋白, 氧化应激, 脂质代谢

Abstract: 【Abstract】　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 normal 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, HDL in serum were examined and the pathological changes were observe in liver tissue by HE, Sirius red.and Sudan Ⅳ. And 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, 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=-0.911and -0.907 respectively, P<0.01). Conclusions The expression of AMPK in hepatic tissue was decreased with the process of ALD, which inhibit the activation to ACC and SREBP. It causes the increase of lipid synthesis, which would result in the fat accumulation in the liver and has a great effect on the liver injury. As a new pharmacological target, AMPK provides a new idea for the prevention and treatment of ALD.

Key words: AMP-activated protein kinase, Acetyl-CoA carboxylase, Sterol regulatory element-binding proteins, Alcoholic liver disease, Oxidative stress, Lipid metabolism

周东方魏峰周俊英. 腺苷酸激活蛋白激酶在大鼠酒精性肝病中的表达减少[J]. 基础医学与临床, 2012, 32(10): 1154-1160.

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