《生命科学》 2014, 26(4): 362-368

能量敏感的AMPK-SIRT1通路与炎症调控

代　洁¹，张晓明²，林　玲³，艾　青⁴，张　力^3*

(1 重庆文理学院校医院，重庆 402160；2 湖北中医药大学针灸骨伤学院， 武汉 430061；3 重庆医科大学病理生理学教研室，重庆 400016；4 重庆医科大学生理学教研室，重庆 400016)

摘　要：腺苷酸活化蛋白激酶(AMP-activated protein kinase， AMPK) 是参与调节细胞能量代谢的关键激酶，也可通过沉默信息调节因子1 (silent information regulator of transcription 1， SIRT1) 依赖的途径发挥抗炎效应。AMPK 激活SIRT1 的机制在于AMPK 促进了SIRT1 的激活因子NAD+ 的生成，并解除了DBC1 对SIRT1活性及p53 对SIRT1 表达的抑制效应；而SIRT1 则通过催化NF-κB、AP-1 和组蛋白的去乙酰化反应而降低转录因子活性、恢复染色质致密构象，这可抑制炎症相关基因的转录。此外，AMPK 激活剂及临床常用降糖药二甲双胍均可通过激活AMPK 而在多种炎症相关性疾病模型中发挥有效保护作用。因而，AMPKSIRT1通路有望成为抗炎治疗的新靶点。

Energy-sensitive AMPK-SIRT1 pathway and the regulation of inflammation

DAI Jie¹， ZHANG Xiao-Ming²， LIN Ling³， AI Qing⁴， ZHANG Li^3*

(1 Hospital of Chongqing University of Arts and Sciences， Chongqing 402160， China; 2 College of Acupuncture and Orthopedics， Hubei University of Chinese Medicine， Wuhan 430061， China; 3 Department of Pathophysiology， Chongqing Medical University， Chongqing 400016， China; 4 Department of Physiology， Chongqing Medical University， Chongqing 400016， China)

Abstract: AMP-activated protein kinase (AMPK) is a crucial kinase involved in the modulation of cellular energy metabolism， and it also has SIRT1-dependent anti-inflammatory activity. The mechanisms through which AMPK activate SIRT1 include promoting the generation of SIRT1 activator NAD+， relieving the suppressive effects on the activity of SIRT1 by DBC1 and on the expression of SIRT1 by p53. SIRT1 then modulates the inflammatory response through deacetylating nuclear factor kappa B (NF-κB)， activator protein 1 (AP-1) and histones， thus leading to suppressed transcriptional activities of transcription factors， altered conformation of chromatin， and eventually， transcriptional repression of inflammation-related genes. In addition， AMPK activator and the clinic antidiabetic metformin have protective benefits in various animal models with inflammation-related disorders through activating AMPK. Thus， AMPK-SIRT1 pathway might become a novel target for anti-inflammatory therapy.