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目的比较卡维地洛(CAR)、美托洛尔(MET)和特拉唑嗪(TER)对超压力负荷下心肌组织钙调神经磷酸酶(calc ineurin,CaN)通路的影响,并探讨CAR改善心肌重构的机制。方法以腹主动脉缩窄法建立大鼠超压力负荷模型。大鼠分为5组,每组10只,即手术组、CAR干预组、MET干预组、TER干预组及假手术组。采用免疫沉淀法检测左心室心肌组织中CaN、活化的T细胞核因子(NFAT3)、锌指转录因子(GATA4)的磷酸化及其蛋白的表达以及c-myc蛋白的表达。结果与假手术组相比,术后14 d,左室心肌明显肥厚,CaN、GATA4磷酸化增强、c-myc蛋白表达增加(P<0.01),NFAT3磷酸化减弱;CAR明显改善左室肥厚,MET次之,而TER的作用不明显。CAR干预组大鼠左室心肌中CaN、GATA4的磷酸化较手术组减弱,c-myc蛋白的表达较手术组减弱(P<0.01),MET次之(P<0.01),而TER作用不明显。结论CAR与MET均能明显改善左心室的肥厚,其作用机制可能与通过抑制了CaN信号通路进而抑制心肌肥厚的相关基因c-myc的表达有关。
Objective To compare the effects of carvedilol (CAR), metoprolol (MET) and terazosin (TER) on the expression of calcineurin (CaN) Mechanisms to improve myocardial remodeling. Methods A rat model of overpressure was established by abdominal aorta constriction. The rats were divided into 5 groups, 10 in each group, namely operation group, CAR intervention group, MET intervention group, TER intervention group and sham operation group. Immunocytochemistry was used to detect the phosphorylation and protein expression of CaN, NF-κB, GATA4 and c-myc in left ventricular myocardium. Results Compared with sham operation group, left ventricular myocardial hypertrophy, CaN and GATA4 phosphorylation increased, c-myc protein expression increased (P <0.01) and NFAT3 phosphorylation decreased on the 14th day after operation. CAR significantly improved left ventricular hypertrophy, MET followed by the role of TER is not obvious. The phosphorylation of CaN and GATA4 in the left ventricular myocardium of CAR group was weaker than that of the operation group, the expression of c-myc protein was weaker than that of the operation group (P <0.01), followed by MET (P <0.01), while the effect of TER was insignificant . Conclusion Both CAR and MET can significantly improve the left ventricular hypertrophy. The mechanism may be related to the expression of c-myc, a gene that inhibits cardiac myocyte hypertrophy by inhibiting CaN signaling pathway.