不同肾上腺素能受体阻滞剂对超压力负荷大鼠左室重构的影响

Effect of different adrenergic receptor antagonists on left ventricular remodeling of hypertension loaded in rats

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。

AIM To compare the effect of carvedukik （CAR）, metoprolol （MET） and terazosin （TER） on calcinurin （CAN） pathway of cardiac muscle tissue under hypertension load and to explore the mechanism of myocardium remodeling improved by CAR. METHODS A model of hypertension loaded rats was established by coarctation of abdominal aorta （CAB） operation. Fifty Wistar rats were divided randomly into five groups, namely, CAB operation group, CAR intervention group, MET intervention group, TER intervention group and sham operation group. Immunoprecitipation was used to determine phosphorylation and expression of CaN, NFAT3, GATA4 and expression of c-myc protein in myocardial tissues. RESULTS Hypertrophy of left ventricular myocardium was observed clearly 14 days after operation. Phosphorylation and expression of CaN and GATA4, and their expression of c-myc were stronger than those of sham operation group （ P 〈 0. 01 ）. However, phosphorylation of NFAT3 was lower than that of sham-operation group. For left ventricular remodeling, CAR was significantly better than MET, but TER almost had no effect. Phosphorylation of CaN and GATA4 and expression of c-myc protein in CAR group were lower than those in MET group （P 〈0. 01 ）, but they were higher in MET group compared with those in TER group （P 〈0. 01 ）. No marked differences were found between CAB and TER groups. CONCLUSION CAR and MET can distinctly improve myocardium hypertrophy of hypertenssion loaded rats, possibly by inhibition of caIcineurin singal pathway.