腺苷酸活化蛋白激酶：炎症调控新靶点 - 生理学报.pdf

生理学报Acta Physiologica Sinica , June 25, 2012, 64(3): 341–345 341 综 述 腺苷酸活化蛋白激酶：炎症调控新靶点 1,2 1 2,* 姚烽 ，汲广岩 ，张力 1 2 400016 重庆医科大学 临床学院；病理生理学教研室，重庆 摘 要：腺苷酸活化蛋白激酶(AMP-activated protein kinase, AMPK)是参与调节糖、脂肪和蛋白质的代谢，维持细胞能量稳态 / AMPK SIRT1 PGC-lα p53 FoxO3a -κB 的关键丝氨酸苏氨酸蛋白激酶。新近研究表明： 可通过磷酸化 、 、 和 等下调核因子 的活 性、抑制炎症相关基因的表达并减轻组织炎症损伤；此外，临床常用的降糖药二甲双胍也可通过激活AMPK而减轻炎症损 伤。因而，AMPK将成为极具前景的抗炎药物开发新靶点。本文就AMPK 的炎症调控效应及其分子机制作一综述。 -κB 关键词：腺苷酸活化蛋白激酶；炎症；核因子 ；二甲双胍 中图分类号：R364.5 ；Q55 AMPK: a novel target controlling inflammation 1,2 1 2,* YAO Feng , JI Guang-Yan , ZHANG Li 1 2 College of Clinical Medicine; Department of Pathophysiology, Chongqing Medical University, Chongqing 400016, China Abstract: The AMP-activated protein kinase (AMPK) is a pivotal serine/threonine kinase participating in the regulation of glucose, lipid as well as protein metabolism and maintenance of energy homeostasis. Recent studies demonstrated that AMPK can also inhibit nuclear factor-κB, suppress the expression of inflammatory genes and attenuate inflammatory injury through phosphorylating its downstream targets including SIRT1, PGC-lα, p53 and FoxO3a. In addition, the widely used antidiabetic metformin also exerts its anti- inflammatory effects through activating AMPK. Therefore, AMPK is emerging as a promising novel target for the development of anti-inflammatory drugs. This review summarized the anti-inflammatory effects of AMPK and the underling molecular mechanisms. Key words: AMP-activated protein kinase; inflammation; nuclear factor-κB; metformin 炎症是机体抵抗病原入侵、修复组织损伤的重 的体内外抗炎效应及其相关分子机制研究的新进 要防御反应，但过度、失控的炎症反应也可造成自 展，分析了AMPK 在炎症发生发展中的重要作用，