摘要
目的探讨超压力负荷左心室心肌β1受体、β2受体和β3受体mRNA表达及钙调神经磷酸酶(Calcineurin,CaN)通路的变化,及美托洛尔改善心肌重构的机制。方法用腹主动脉缩窄法建立大鼠超压力负荷模型,手术组、美托洛尔组及假手术组各10只。用免疫沉淀法检测左心室心肌CaN、活化T细胞核因子(nuclear factor-3 of activated T cells,NFAT3)、锌指转录因子4(zinc finger transcription factor-4,GATA4)磷酸化及蛋白表达以及原癌基因c-myc蛋白表达。结果大鼠术后14d左心室明显肥厚,手术组β1受体mRNA表达较假手术组明显减少(P<0.01),美托洛尔组β1受体mRNA表达明显回升,美托洛尔组与手术组差异有统计学意义(P<0.01);各组间β2受体mRNA表达差异无统计学意义;手术组β3受体mRNA表达较假手术组增加,美托洛尔组与手术组相比差异无统计学意义,与假手术组相比。CaN、GATA4磷酸化增强、c-myc蛋白表达增加(P<0.01),NFAT3磷酸化减弱,美托洛尔明显改善左心室肥厚。结论美托洛尔能明显改善左心室肥厚,其作用机制可能与抑制了CaN信号通路有关。
Objectives To investigate the alteration of expressions of β1, β2, β3-adrenoceptor mRNA and calcineufin （CAN） signal pathway in left ventricular hypertrophy subsequent to coarctation of abdominal aorta in rats, and to elucidate the effects and new mechanism of metoprolol （MET） on cardiac remodeling regression. Methods A model of left ventricular hypertrophy induced by coarctation of abdoninal aorta （CAB） was used in this study. Wistar rats were divided randomly into five groups （n =10）, namely CAB group, CAR group, MET group, TER group and sham operation group. Immunoprecitipation was used to assay the protein expression and phosphorylation of CaN, nuclear factor 3 of activated T cells （NFAT3） , zinc finger trans- cription factor-4 （GATA4） , c-myc protein expression in myocardial tissues; mRNA expression of β1, β2, β3-adrenoceptor in myocardial tissue were analyzed by reverse transcriptase-polymerase chain reaction （RT- PCR）. Results Left ventricular myocardium hypertrophy was observed clearly 14 days after operation, β1- adrenergic receptor mRNA expressaions in myocardial tissue were significantly lower in operation group than that in sham-operation （P 〈 0.01） , but higher than that in MET group. β3-adrenergic receptor mRNA expressons in myocardial tissue were significantly higher in patients with operation group than those in sham-operation group group, but much higher than that in MET group （P〈 0.01）. No differences were observed in β2-adrenergic receptor mRNA expressons among three groups （P 〉 0.05）. Phosphorylation of CaN, GATA4 and protein expression of c-myc were stronger than those of sham-operation group （P 〈 0.01） ; On the contrary, phosphorylation of NFAT3 was lower than that of sham-operation group. MET could meliorate left ventricular remodeling significantly. Conclusions MET can improve myocardium hypertrophy in overloaded pressure rat models, the pathogenesis may be related to the inhibition of calcineurin singal pathway.
出处
《岭南心血管病杂志》
2008年第1期63-66,共4页
South China Journal of Cardiovascular Diseases
关键词
肾上腺素受体
肥大
左心室
钙调神经磷酸酶
信号转导
β-Adrenergic receptors
hypertrophy, left ventricle
caleineurin
signal transduction
