有氧运动通过AMPKα调控高血压肠系膜动脉平滑肌CaL通道功能  

Aerobic Exercise Regulates the Function of CaL Channel via AMPKαin Hypertensive Mesenteric Artery Smooth Muscle

作　　者：单美玲 陈渝[1] 周杨 刘霜 顾博雅 李丽[1,2] 石丽君 SHAN Mei-Ling;CHEN Yu;ZHOU Yang;LIU Shuang;GU Bo-Ya;LI Li;SHI Li-Jun(Department of Exercise Physiology,Beijing Sport University,Beijing 100084,China;Key Laboratory of Physical Fitness and Exercise,Ministry of Education,Beijing Sport University,Beijing 100084,China)

机构地区：[1]北京体育大学运动生理教研室,北京100084 [2]北京体育大学运动与体质健康教育部重点实验室,北京100084

出　　处：《中国生物化学与分子生物学报》2020年第10期1199-1209,共11页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金(No.31771312,No.32071174);中央高校基本科研业务费专项资金(No.2020049)资助。

摘　　要：腺苷酸激活蛋白激酶(AMP-activated protein kinase,AMPK)被称为细胞能量代谢调节器,其α亚基主要起催化作用,同时也是大鼠血管壁细胞的主要激酶形式。除能量代谢外,AMPKα还可参与调控高血压的发生和发展,但其具体的作用机制尚不完全清楚。本研究拟以自发性高血压大鼠(spontaneously hypertensive rat,SHR)肠系膜动脉为研究对象,探究AMPKα对肠系膜动脉舒张功能的影响,并阐述其作用机制。选取12周龄雄性正常血压大鼠(Wistar-Kyoto,WKY)和SHR,将其随机分为安静对照组(WKY-SED,SHR-SED)和有氧运动组(WKY-EX,SHR-EX)。有氧运动组进行为期12周的中等强度跑台运动。测定各组大鼠实验前后体重、血压,随后通过微血管张力技术、膜片钳技术、Western印迹分别测定AMPKα对血管张力的影响,AMPKα与L型电压依赖性钙离子通道(voltage-dependent L-type Ca2+channel,CaL)的关系,以及p-AMPKα和AMPKα的表达水平。结果显示,有氧运动后,高血压大鼠体重、血压均显著降低(P<0.05);微血管张力技术测定结果表明,AMPKα特异性激动剂PT1可诱使各组血管舒张。其中,SHR-SED组舒张程度显著高于WKY-SED(P<0.05)。与SHR-SED组相比,SHR-EX组血管舒张程度显著降低(P<0.05),与WKY-SED组相比,WKY-EX组舒张程度显著增加(P<0.05)。进一步对AMPKα的作用机制进行探究发现:PT1可抑制CaL通道电流,其中,SHR-SED组CaL通道电流降低幅度显著高于WKY-SED组(P<0.05),12周有氧运动后,SHR-EX组电流幅值降低幅度显著减小(P<0.05),WKY-SED组与WKY-EX间无显著性差异(P>0.05);Western印迹结果显示,SHR-SED组p-AMPKα表达显著减少(P<0.05)。12周干预后,WKY-EX、SHR-EX组p-AMPKα表达均显著增加(P<0.05),但各组间AMPKα表达无显著差异(P>0.05)。其总的结果表明,有氧运动通过激活AMPKα抑制高血压肠系膜动脉平滑肌细胞CaL通道功能,从而改善高血压阻力动脉的舒张功能,降低血压。AMP-activated protein kinase(AMPK)is known as a regulator of cellular energy metabolism.Its alpha subunit mainly plays a catalytic role,and is also the main kinase form of rat vascular wall cells.In addition to metabolism,AMPKαcan also participate in regulating the occurrence and development of hypertension,but its specific mechanism is not fully understood.This study intends to explore the effects of AMPKαon the diastolic function of mesenteric arteries in spontaneously hypertensive rats(SHR)mesenteric arteries,and to elaborate its mechanism of action.Twelve-weeks-old,male,Wistar-Kyoto(WKY)and SHR were randomly divided into sedentary groups(WKY-SED,SHR-SED)and exercise training groups(WKY-EX,SHR-EX),respectively.The exercise training groups underwent moderateintensity treadmill running for 12 weeks.The body weight and blood pressure of rats in each group were measured before and after the experiment,and then the effects of AMPKαon vascular tone,the relationship of AMPKαand L-type voltage-dependent calcium channels(CaL)and the expression levels of p-AMPKαand AMPKαwere measured by using isometric contraction test,the whole-cell patch clamp technique and Western blot.After aerobic exercise intervention,the weight and blood pressure of hypertensive rats were significantly reduced(P<0.05);the results of isometric contraction study showed that AMPKαspecific agonist PT1 can induce vasodilation in each group,the degree of relaxation in the SHR-SED group was significantly higher than that in WKY-SED(P<0.05);Compared with the SHRSED group,the SHR-EX group vasodilator response was significantly reduced(P<0.05),and the WKYEX group had a significantly higher degree of relaxation than the WKY-SED group(P<0.05).Further investigation of the mechanism of AMPKαrevealed that PT1 can inhibit the CaL channel current;among them,the reduction of CaL channel current in SHR-SED group is significantly higher than that in WKYSED group(P<0.05).After exercise intervention,the current amplitude decreased significantly in the SHR-EX g

关 键 词：有氧运动 高血压 L型电压依赖性钙离子通道 腺苷酸激活蛋白激酶α亚基 肠系膜动脉 

分 类 号：G804.5[文化科学—运动人体科学]