AICAR和二甲双胍对产蛋鸡肝细胞AMPK活性及脂质代谢的影响

Effects of AICAR and Metformin on AMPK Activity and Lipid Metabolism in Laying Hens' Primary Cultured Hepatocytes

以产蛋鸡肝细胞为材料,研究添加腺苷一磷酸激活的蛋白激酶(AMPK)激活剂AICAR和治疗二型糖尿病药物———二甲双胍对产蛋鸡肝细胞AMPK、β-羟基-β-甲基戊二酸单酰辅酶A还原酶(HMGR)、乙酰辅酶A羧化酶(ACC)和细胞脂质代谢的影响。试验分4个处理:基础培养液组(对照组)、基础培养液组中分别加入0.5mmol/L AICAR、0.5 mmol/L二甲双胍1、mmol/L二甲双胍。结果表明,肝细胞培养100 min时,AICAR和二甲双胍均可激活AMPK(P<0.05),且二甲双胍激活AMPK具有一定的浓度依赖性;AICAR和二甲双胍均可不同程度抑制脂肪酸和胆固醇合成的关键酶ACC和HMGR的活性,AMPK活性与HMGR、ACC活性呈一定的负相关;添加AICAR和二甲双胍抑制产蛋鸡肝细胞甘油三酯和胆固醇合成,AMPK活性与肝细胞甘油三酯和总胆固醇含量也呈一定的负相关。因此,可通过调控产蛋鸡肝脏AMPK活性变化从而调节产蛋鸡脂肪和胆固醇的合成。

The effects of 5-amino-4-imidazolecarboxamide riboside （AICAR）and the antidiabetic drug metformin on AMP-activated protein kinase （AMPK） activity and its downstream effector, acetyl-CoA carboxylase （ ACC）, β-hydroxy-β-methylglutary-CoA reductase （HMGR） activities in laying hens＇ primary cultured hepatocytes were studied. Four treatments were employed in this experiment. AICAR （0. 5mmol/L）, metformin （0. 5mmol/L）, and metformin （1mmol/L） were added respectively into the standard culture medium（control）. At 100 min after incubation, AICAR or metformin activated AMPK significantly （ P〈0.05）, inactivated ACC and HMGR which are the major enzymes involved in fatty acid and cholesterol biosyntheses. AMPK regulated ACC and HMGR activities negatively. AICAR or metformin decreased hepatic lipid and cholesterol contents by activating AMPK . AMPK negatively regulated hepatic lipid and cholesterol contents. These findings suggest that the regulation of hepatic lipid and the cholesterol metabolism of primary hepatocytes in laying hens can be mediated by AMPK .