%0 Journal Article %T 过氧化氢酶:二甲双胍药理效应新靶点?
Catalase: a novel pharmacological target of metformin? %A 乐波 %A 葛璞 %A 艾青 %A 林玲 %A 张力 %J 医学争鸣 %D 2015 %X 降糖药二甲双胍(MET)具有降糖、抗炎等多种药理学效应,这些效应主要依赖于腺苷酸活化蛋白激酶(AMPK)。但我们近期发现MET也可通过AMPK非依赖的方式直接结合过氧化氢酶(CAT)并增强CAT活性。我们推测这可能是MET发挥效应的新机制,并在小鼠内毒素性肝炎模型上开展了系列研究。结果发现:MET在减轻内毒素性肝炎的同时可增强肝内CAT活性、且CAT在内毒素性肝炎中发挥保护效应,但CAT抑制剂并不能消除MET对内毒素性肝炎的保护效应,MET激活CAT的效应在内毒素性肝炎中无重要药理意义。因而,CAT是否为MET药效新靶点有待进一步研究。
The antidiabetic agent metformin (MET) has hypoglycemic, anti-inflammatory and anti-tumor activities,which largely depends on AMP-activated protein kinase (AMPK). However, our recent studies found that MET directlybound with catalase (CAT) and enhanced the activity of CAT in an AMPK-independent manner. We supposed that CATmight be a novel target of MET and this hypothesis was tested in a mouse model with endotoxic hepatitis. We found thatMET enhanced the activity of hepatic CAT and attenuated endotoxic hepatitis, and that CAT provided protective benefitsagainst endotoxic hepatitis. However, CAT inhibitor did not reverse the protective effects of MET against endotoxichepatitis. The activation of CAT seemed not important for the protective effects of MET. Therefore, whether CAT acts as anovel pharmacological target of MET remains to be further investigated %K 二甲双胍 %K 过氧化氢酶 %K 氧化应激 %K 肝炎 %K 炎症
metformin %K catalase %K oxidative stress %K hepatitis %K inflammation %U http://yxzm.paperonce.org/oa/DArticle.aspx?type=view&id=201502004