缬沙坦对心衰大鼠心肌GLUT4表达的影响及机制探讨(1)
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【摘要】目的 观察不同剂量缬沙坦对心衰大鼠心肌GluT4表达的影响并探讨其可能机制。方法 将30只SD大鼠随机分为对照组、模型组和缬沙坦高(30 mg·kg-1·d-1)、中(15 mg·kg-1·d-1)、低(7.5 mg·kg-1·d-1)剂量组各6只。后四组大鼠缩窄腹主动脉，制备慢性心力衰竭模型。按要求灌胃饲养8周后，观察指标。结果 与对照组相比，腹主动脉缩窄大鼠心肌细胞Glut4及AMPK-α蛋白水平下降、BNP升高，差异显著。与模型组相比，缬沙坦各剂量组大鼠心肌细胞Glut4及AMPK-α蛋白水平升高，差异显著。高剂量组升高更明显。结论 腹主动脉缩窄术后8周大鼠心肌GluT4明显降低；缬沙坦治疗后增加心肌GluT4蛋白水平，其机制可能与增强AMPK-α表达有关。
【关键词】缬沙坦 慢性心力衰竭 左室重塑 GluT4AMPK-α
中图分类号：R285.5文献标识码：B文章编号：1005-0515(2011)3-076-02
Effects and Mechanisms of Valsartan on Expression of Glucose Transporter 4in Cardiac Muscle Tissue of the modelrats of heart failure
【Abstract】Objective To observe effects and mechanisms of different doses of valsartan on expression of Glucose Transporter 4 in Cardiac Muscle Tissue of the modelrats of heart failure.MethodsHeart failure induced by abdominal aorta constriction were randomly divided into model group ( n =6) and valsartan group (High dose:30mg/Kg, once /daily, n = 6. Medium dose:15mg/Kg, once /daily, n = 6.Low dose:7.5mg/Kg, once /daily, n = 6) ,another normal rats were served as control group ( n=6) .After eight weeks treatment, general status, damaging changes in histomorphology of cardiac muscle in rats and ventricular remodeling were observed; the level of Glut4、AMPK-α and BNP were measured. ResultsIn model group, the level of Glut4 and AMPK-α were remarkably reduced. There were significant differences in level of Glut4 and AMPK-α between valsartan group and model group. Especially in the high dose ones. ConclusionValsartan increased the level of Glut4 in cardiac muscle tissue ofthe modelrats of heart failure; The underlying mechanism is possibly attributed to its effect in up-regulating the expression of AMPK-α.
【Key words】Valsartan Heart Failure Ventricular remodeling Glut4,AMPK-α
心力衰竭是各种心脏疾病发展的终末阶段。心力衰竭时心肌细胞衰竭是由底物代谢改变造成的，即心肌细胞脱离脂肪酸代谢而向碳水化合物的氧化代谢转变。改善心肌能量代谢障碍要以促进糖代谢和抑制脂肪酸代谢为主要目标。
葡萄糖转运蛋白4(Glucose Transporter 4，GluT4)是一种胰岛素敏感性葡萄糖转运蛋白，其介导葡萄糖进入细胞是心肌细胞内糖代谢的第一个限速步骤。因此GluT4的表达、转位与病理状态下心肌能量代谢密切相关。腺苷酸活化蛋白激酶(AMP-activated protein kinase，AMPK)作为细胞能量状态的感受器和调节器在维持细胞能量稳态和适应性反应中扮演关键角色[1]。AMPK是一个异三聚体，由具有催化作用的α亚基和具有调节作用的β和γ亚基构成。研究表明，在缺血心肌组织中，GluT-4转位和葡萄糖摄取增加因AMPK的激活而增加 [2][3] ......
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