非诺贝特和吡格列酮干预对代谢综合征大鼠心肌重构的影响

Effects of fenofibrate and pioglitazone on cardiac remodeling in rats with metabolic syndrome

目的探讨非诺贝特和吡格列酮对果糖诱导的代谢综合征大鼠心脏重构的影响。方法用高果糖饮食饲养SD大鼠构建代谢综合征大鼠模型;成模后大鼠继续用高果糖饮食喂养,并分为4组:模型对照组,非诺贝特组,吡格列酮组,非诺贝特加吡格列酮组,分别加用相应药物干预4周。比较干预后组间大鼠心脏肥厚指数及心肌结构上的差异。结果高果糖饮食可成功诱导具有高血压、高甘油三酯血症、高胰岛素血症等特征的代谢综合征大鼠模型;该大鼠模型心肌肥厚指数较对照组大鼠增加([3.93±0.26)v(s3.12±0.24)mg/g,P<0.01)],心肌细胞肥大,结构紊乱。与模型对照组大鼠比较,非诺贝特组、吡格列酮组及非诺贝特加吡格列酮组大鼠心肌肥厚指数均降低([3.61±0.28)v(s 3.93±0.26)mg/g,P<0.05;(3.53±0.21)v(s 3.93±0.26)mg/g,P<0.01;(3.30±0.18)v(s3.93±0.26)mg/g,P<0.01],心肌结构有所改善;与非诺贝特组大鼠比较,非诺贝特加吡格列酮组大鼠心肌肥厚指数进一步降低([3.30±0.18)v(s3.61±0.28)mg/g,P<0.01],心肌结构明显改善。结论非诺贝特和吡格列酮干预均可抑制代谢综合征大鼠心肌的病理性重构,合用非诺贝特和吡格列酮,效果更明显。

【Objective】 To explore the effects of fenofibrate and pioglitazone on cardiac remodeling in the fructose-induced metabolic syndromic rats.【Methods】 Metabolic syndrome was induced in 44 male Sprague-Dawley rats by feeding high fructose（60% fructose） diet for 10 weeks.Then model rats of metabolic syndrome were still fed with 60% fructose diet,and were divided into 4 groups： model control group（MC group）,no medication was given;fenofibrate group（FEN group）,were treated with fenofibrate [30 mg/（kg·d）],pioglitazone group（PIO group）,were treated with pioglitazone [3 mg/（kg·d）],and fenofibrate plus pioglitazone group（FEN＋PIO group） were treated with fenofibrate [30 mg/（kg·d）] and pioglitazone [30 mg/（kg·d）] for 4 weeks.Another 10 male Sprague-Dawley rats constituted control group（NC group） and constantly consumed standard rat chow.The differences in index of myocardial hypertrophy and myocardial morphosis were analyzed between groups after intervention.【Results】 High fructose diet successfully induced a model rat with metabolic syndrome,characterized by a significant increase in systolic blood pressure,serum triglycerides,free fatty acids and insulin compared with the control group.In addition,the index of myocardial hypertrophy of this model was increased [（3.93 ± 0.26） vs（3.12 ± 0.24） mg/g,P 0.01],and with a hypertrophic and disordered myocardial compared with control group.Treatment with fenofibrate,pioglitazone,and fenofibrate plus pioglitazone all decreased the index of myocardial hypertrophy of rats with metabolic syndrome [（3.61 ±0.28） vs（3.93 ± 0.26） mg/g,P 0.05;（3.53 ± 0.21） vs（3.93 ± 0.26） mg/g,P 0.01,（3.30 ± 0.18） vs（3.93 ± 0.26） mg/g,P 0.01],and amended their myocardic remodeling.Compared to fenofibrate group,rats in fenofibrate plus pioglitazone group exhibited a less index of myocardial hypertrophy [（3.30 ± 0.18） vs（3.61 ± 0.28） mg/g,P 0.01],and their myocardial morphosis was improved significantly.【Conclusions】 Treatment with fenofibrate or pioglitazone singly can amend myocardial pathologic remodeling in rats with metabolic syndromic,but the effects are more significant when treated by combining with fenofibrate and pioglitazone.