衰竭心肌能量代谢重构及β_3肾上腺素能受体、过氧化物酶体增殖物激活受体仪表达变化的研究

Expressions of β_3-adrenoceptor and peroxisome proliferator-activated receptor α in human failing heart

目的通过检测衰竭与健康心肌组织代谢底物含量、相关酶活性及β_3肾上腺素能受体、过氧化物酶体增殖物激活受体α(PPARα)基因和蛋白表达的变化,探讨衰竭心肌代谢重构的表现及可能机制。方法选取6例意外伤亡健康者心肌组织和20例心外科瓣膜置换术的心力衰竭患者,检测心肌游离脂肪酸(FFA)、乳酸(LD)含量和 ATP 酶活力。应用逆转录聚合酶链反应、Western blot和免疫组化法分别检测心肌组织β_3受体和 PPARα mRNA 表达以及蛋白和定位。结果衰竭心肌FFA 和 LD 含量明显增加(P<0.01和 P<0.05)。Na^+K^+-ATP 酶和 Ca^(2+)Mg^(2+)-ATP 酶活性则显著降低(P<0.05和 P<0.01)。衰竭心肌β_3肾上腺素能受体 mRNA 和蛋白表达明显高于正常心肌,而PPARα表达则显著低于正常心肌,但并未发生定位变化。结论心力衰竭时存在代谢重构,表现为心肌代谢底物发生转变,代谢相关酶活性下降等,β_3肾上腺素能受体和 PPARα在衰竭心肌分别上调和下调,可能参与心肌组织代谢重构。

Objective To explore the changes on the content of substrate, the activity of correlative enzyme and the mRNA and protein expressions of β3-adrenoceptor and peroxisome proliferator-activated receptor α （PPARα） in human failing heart. Method Papillary muscles from 20 patients with heart failure during mitral valves replacement and 6 control subjects died of non-cardiac accidents were obtained and free fat acid （FFA）, lactic acid （LD） and the activity of Na^＋K^＋ -ATPase and Ca^2＋ Mg^2＋ -ATPase, protein and mRNA expressions of β3-adrenergic receptor and PPARα were measured. Result In the failing heart, the contents of fat acid, LD and expression of β3-adrenceptor mRNA and protein were significantly higher while the activity of Na^＋K ^＋-ATPase and Ca^2＋ Mg^2＋ -ATPase, expressions of PPARα at mRNA and protein levels were significantly lower than those in control myocardium. Conclusion Metabolic remodeling （upregulation of β3- adrenoceptor and downregulation of PPARα） might contribute to the pathophysiology of heart failure.