摘要
目的探讨二甲双胍对心力衰竭(心衰)大鼠心功能的影响并对其可能的作用机制进行分析。方法利用阿霉素多次间断腹腔给药方法建立心力衰竭模型,分为二甲双胍治疗组15只、5-氨基咪唑-4-甲酰胺核糖核苷酸(5-amino-imidazole-4-carboxamide ribose nucleotides,AICAR)治疗组15只、生理盐水对照组15只,并设正常组10只,4周后分别观察左心室射血分数(left ventricular ejection fraction,LVEF)、血流动力学指标、血浆B-型脑钠肽值(B-type natriuretic peptide,BNP),并留取心肌组织进行免疫组织化学分析。结果与心衰盐水对照组比较,二甲双胍灌胃组、AICAR注射组4周后LVEF、左室收缩末压(left ventricular systolicpressure,LVSP)和左室内压最大变化速率(left ventricular maximum velocity of ascending and descending inintraventricular pressure,±dp/dtmax)均显著提高,同时左室舒张末压(left ventricular end-diastolic pressure,LVEDP)显著降低(P<0.05)。与正常对照组比较,所有的阿霉素腹腔注射大鼠血BNP含量明显升高(P<0.05)。心衰大鼠二甲双胍灌胃及AICAR注射4周后,与生理盐水对照组比较血BNP浓度明显降低(P<0.05)。心室肌细胞免疫组织化学结果示活化的腺苷激活的磷酸化酶-2(phosphorylation of AMP-activated protein kinase,P-AMPKα2)及内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)在二甲双胍及AICAR治疗组明显高表达(P<0.05),而二甲双胍和AICAR组之间差异无统计学意义。结论二甲双胍可明显抑制心衰大鼠心功能的恶化,这种作用可能和激活腺苷激活的磷酸化酶(AMPK)及后续的eNOS有关。
[Objective] To investigate the effect of metformin on left ventricular (LV) function in Adriamyein-induced heart failure models of Wistar rats. [Methods ] Heart failure was induced by injection of Adriamyein (4 mg/kg) through abdominal cavity once a week in Wistar rats. Animals were randomly divided into control (n =15), mefformin (100 mg/kg once daily, n =15), 5-amino-imidazole-4-carboxamide ribose nucleotides (AICAR, 5 mg/kg, sc, every second day, n =15) and normal (n =10). After 4 weeks, LV function was assessed by echocardiography, hemodynamic monitoring and plasma B-type natriuretic peptide (BNP). Immunohistopathological examination was performed to evaluate the expression of phosphorylation of AMP- activated protein kinase-2 (P-AMPK-2) and endothelial nitric oxide synthase (eNOS) in the ventricular myocytes. [Results] At the end of 4 weeks treatment, the LV systolic pressure (LVSP), LV maximum velocity of ascending and descending in intraventrieular pressure (±dp/dtmax) and LV ejection fraction (LVEF) in the mefformin and AICAR groups were higher than those in the control group, left ventricular end-diastolic pressure (LVEDP) was lower (P〈0.05). The mean BNP in the metformin and AICAR groups was lower than that in the control group (P 〈0.05). The mean values of P-AMPK-2 and eNOS expression in the metformin and AICAR were similar (P〉0.05), but were greater than those in the control group (P 〈0.05). [Conclusion] Metformin treatment prohibited the progression of LV function in rats with Adriamycin-induced heart failure. This functional improvement is associated with an increased expression of AMPK and eNOS in the ventricular myocytes.
出处
《中国现代医学杂志》
CAS
CSCD
北大核心
2012年第2期20-24,共5页
China Journal of Modern Medicine
基金
河南省医学科技攻关计划项目(No:201003021)