AMPK通过增强心肌脂肪酸氧化抑制大鼠心肌肥厚  

Activated AMPK attenuates cardiac hypertrophy in rats through increasing myocardial fatty acid oxidation

作　　者：殷然[1] 董吁钢[1] 李红良[2] 刘丹[1] 

机构地区：[1]中山大学附属第一医院心内科,广东广州510080 [2]中国医学科学院基础医学研究所,北京100005

出　　处：《中国病理生理杂志》2007年第7期1258-1262,共5页Chinese Journal of Pathophysiology

基　　金：广东省自然科学基金项目资助(No31748)

摘　　要：目的:探讨单磷酸腺苷(AMP)激活的蛋白激酶(AMPK)对心肌肥厚的影响及可能涉及的作用机制。方法:通过对大鼠行腹主动脉缩窄术(TAC)引起压力负荷增加,造成心肌肥厚的模型。术后24h起经皮下注射AMPK的特异性激活剂AICAR(0.5mg.kg-1.d-1)直至术后7周。处死动物前,对大鼠进行超声心动学指标的检测和血清游离脂肪酸浓度测定;处死动物,取心脏称重后计算心脏重/体重比值,测量心肌细胞的平均直径、心肌中的游离脂肪酸含量、过氧化体增殖物激活型受体α(PPARα)和肉碱棕榈酰转移酶(CPT-I)的mRNA表达。结果:(1)心肌肥厚+AICAR组大鼠的心脏重/体重比值、心肌细胞平均直径、血清及心肌中游离脂肪酸的浓度明显低于心肌肥厚对照组;(2)心肌肥厚+AICAR组大鼠心肌PPARα及CPT-I的mRNA表达明显高于心肌肥厚对照组;(3)心肌肥厚+AICAR组大鼠心脏超声心动学指标:左室后壁舒张末期厚度、左室舒张、收缩末期内径(PWT,LVDD,LVSD)低于心肌肥厚对照组,左室短轴缩短率(FS%)则高于心肌肥厚对照组。结论:活化的AMPK可能通过增强心肌脂肪酸氧化从而抑制压力负荷增加引起的心肌肥厚。AIM： To investigate the antihypertrophic function of adenosine monophosphate -activated protein kinase （AMPK） and its effects on myocardial fatty acid oxidation. METHODS ： The model of cardiac hypertrophy was produced by banding abdominal aorta （ transaortic constriction, TAC ） in male Sprague - Dawley rats. 5 - aminoimidazole - 4 - carboxamide ribonucleoside（ AICAR ）, a pharmacological activator of AMPK, was injected subcutaneously （0. 5 mg ·kg^-1·d^-1 ） 24 hours after operation and continued till 7 weeks after operation. Echocardiographic and ventricular remodeling parameters, free fatty acid concentration in blood serum and myocardium, and expression of peroxisome proliferator - activated receptor（PPARct） and carnitine palmityl transferase（ CPT- I） mRNA were investigated after treatment of AICAR or vehicle for 7 weeks. RESULTS ： Compared with control group, treatment of rats subjected to TAC with AICAR significantly increased the mRNA expression of PPARα and CPT - I and subsequently decreased free fatty acid concentration in blood and myocardium, improved echocardiographic characteristics, and reduced the increases in the heart weight/body weight ratio and myocyte diameter. CONCLUSION： Pharmacological activation of AMPK may attenuate cardiac hypertrophy through increasing myocardial fatty acid oxidation.

关 键 词：一磷酸腺苷激活的蛋白激酶 心肌肥厚 脂肪酸氧化 线粒体 

分 类 号：R363[医药卫生—病理学]