腺苷酸活化蛋白激酶在纤维化发生中的作用  

Role of AMP-activated protein kinase in fibrogenesis

作　　者：李淑娴 贾强[2] 于功昌[2] 邵华[2] LI Shu-xian;JIA Qiang;YU Gong-chang;SHAO Hua(School of Medicine and Life Sciences,University of Jinan-Shandong Academy of Medical Sciences;Shandong Academy of Occupational Health and Occupational Medicine,Shandong First Medical University&Shandong Academy of Medical Sciences,Jinan 250062,China)

机构地区：[1]济南大学山东省医学科学院医学与生命科学学院 [2]山东省职业卫生与职业病防治研究院,山东第一医科大学(山东省医学科学院),山东济南250062

出　　处：《中国病理生理杂志》2019年第11期2108-2112,共5页Chinese Journal of Pathophysiology

基　　金：山东省重点研发计划项目(No.2016GSF201047; No.2017GSF18186);山东省自然科学基金资助项目(No.ZR2019MH102;No.ZR2016YL015);山东省医学科学院医药卫生科技创新工程;济南市医疗卫生科技计划

摘　　要：腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)被认为是调节能量稳态和代谢应激反应的能量传感器,是一种进化保守的丝氨酸/苏氨酸激酶,由调节性β(β1和β2)和γ(γ1、γ2和γ3)亚单位以及催化性α(α1和α2)亚单位组成[1],其中α亚基含有催化核心的N端激酶结构域(kinase domain,KD),Thr172位点的磷酸化可使AMPK活性增加超过100倍,被认为是AMPK活化的标志。C末端结合β、γ亚基并含有重要的调节结构域,即当AMP水平下降时,可以抑制AMPK活化的自身抑制结构域(autoinhibitory domain,AID)和富含丝氨酸/苏氨酸的结构域“ST环”(ST-loop)[2-3];β亚基的N端有碳水化合物结合模块(carbohydrate-binding module,CBM)将AMPK固定在细胞膜上,而N端区域之后紧跟着α、γ结合区域[4],因此,β亚基相当于1个与α和γ亚基结合的支架,使AMPK形成稳定的异源三聚体[5];γ亚基的N末端包含4个串联的胱硫醚β-合成酶(cystathionineβ-synthase,CBS)重复序列,形成2个可以结合AMP或ATP分子的Bateman结构域[6]。Fibrosis is a common clinical disease that occurs in a variety of organs, and mainly manifests increased connective tissue of organ tissue and decreased parenchymal cells. Continuous progression may lead to organ structural damage, dysfunction and even depletion, seriously threatening human health and life safety. Therefore, in-depth study of the pathogenesis of fibrosis and the development of effective therapeutic drugs are of great importance for the prevention and treatment of fibrosis. Recent studies provide evidence that AMP-activated protein kinase(AMPK) plays an important role in the development of fibrosis. In combination with related literatures, this paper reviews the structure and biological function of AMPK, AMPK in inflammatory response associated with fibrosis, epithelial-mesenchymal transition, extracellular matrix and myofibroblasts, and the therapeutic role of AMPK as a new target in treating fibrosis diseases.

关 键 词：纤维化 腺苷酸活化蛋白激酶 炎症 上皮-间充质转化 细胞外基质 

分 类 号：R363[医药卫生—病理学] R364.5[医药卫生—基础医学]