AMP-activated protein kinase(AMPK), known as a sensor and a master of cellular energy balance, integrates various regulatory signals including anabolic and catabolic metabolic processes.Accompanying the application of...AMP-activated protein kinase(AMPK), known as a sensor and a master of cellular energy balance, integrates various regulatory signals including anabolic and catabolic metabolic processes.Accompanying the application of genetic methods and a plethora of AMPK agonists, rapid progress has identified AMPK as an attractive therapeutic target for several human diseases, such as cancer, type2 diabetes, atherosclerosis, myocardial ischemia/reperfusion injury and neurodegenerative disease. The role of AMPK in metabolic and energetic modulation both at the intracellular and whole body levels has been reviewed elsewhere. In the present review, we summarize and update the paradoxical role of AMPK implicated in the diseases mentioned above and put forward the challenge encountered. Thus it will be expected to provide important clues for exploring rational methods of intervention in human diseases.展开更多
基金supported by grants from National Natural Sciences Foundation of China(NSFC,Grant Nos.81273514,91539126 and81302827)grants from Innovation Engineering of Chinese Academy of Agricultural Sciences(No.125161015000150013)
文摘AMP-activated protein kinase(AMPK), known as a sensor and a master of cellular energy balance, integrates various regulatory signals including anabolic and catabolic metabolic processes.Accompanying the application of genetic methods and a plethora of AMPK agonists, rapid progress has identified AMPK as an attractive therapeutic target for several human diseases, such as cancer, type2 diabetes, atherosclerosis, myocardial ischemia/reperfusion injury and neurodegenerative disease. The role of AMPK in metabolic and energetic modulation both at the intracellular and whole body levels has been reviewed elsewhere. In the present review, we summarize and update the paradoxical role of AMPK implicated in the diseases mentioned above and put forward the challenge encountered. Thus it will be expected to provide important clues for exploring rational methods of intervention in human diseases.
文摘目的探讨脑动脉粥样硬化狭窄分布与急性大动脉粥样硬化性卒中患者早期神经功能恶化(early neurologic deterioration,END)的相关性。方法回顾性纳入2017年3月至2018年5月在安徽医科大学第二附属医院神经内科住院的急性大动脉粥样硬化性卒中患者,END定义为入院72 h内美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale,NIHSS)评分较基线时增加2分,或NIHSS意识水平评分增加1分,或NIHSS运动评分增加1分,或出现任何新发神经功能缺损。患者根据是否发生END分为END组和非END组,根据头颈部CT血管造影、磁共振血管造影或数字减影血管造影确定的脑动脉狭窄情况(狭窄程度>50%)分为单支动脉狭窄组和多支动脉狭窄组。应用多变量logistic回归分析确定END的独立危险因素。结果总共纳入371例患者,其中92例(24.8%)发生END。在单支血管狭窄组中,END发生率因血管狭窄分布而异:大脑前动脉(2.3%)、大脑中动脉(54.4%)、大脑后动脉(9.1%)、基底动脉(4.5%)、颈内动脉颅内段(11.4%)、椎动脉颅内段(6.8%)、颈内动脉颅外段(6.8%)、椎动脉颅外段(4.5%)。END组大脑中动脉狭窄发生率显著高于非END组(54.5%对21.2%;χ^2=17.615,P<0.001)。在多支血管狭窄组中,单纯颅内血管狭窄患者END发生率最高(66.7%),其次为颅内外血管狭窄患者(29.2%),单纯颅外血管狭窄患者最少(4.2%)。END组单纯颅内多支动脉狭窄发生率显著高于非END组(66.7%对47.6%;χ^2=5.262,P=0.022)。多变量logistic回归分析显示,大脑中动脉狭窄(优势比1.805,95%可信区间1.217~2.676;P=0.003)是发生END的独立危险因素。结论急性大动脉粥样硬化性卒中患者的END与脑动脉粥样硬化狭窄分布有关,大脑中动脉狭窄是END的独立危险因素。
