辛伐他汀对心力衰竭家兔左室瞬间外向钾通道表达的影响

Effects of simvastatin on the left ventricular expression of transient outward potassium channel in rabbits with experimental heart failure

目的研究辛伐他汀对心力衰竭(心衰)家兔左室瞬间外向钾通道表达的影响。方法通过结扎家兔冠状动脉左前降支建立心衰模型。随机分成辛伐他汀组(10 mg·kg^(-1)·d^(-1))、心衰组和假手术组。10周后应用超声心动图和有创血流动力学检查进行心室重构及心功能评价。在完成血流动力学指标测定后,立即取出心脏,切取左室远离梗死部位心肌组织液氮冻存。应用半定量-聚合酶链式反应和 Western blot 法检测各组家兔左室电压门控钾通道(K_v 通道)α亚单位 K_v 1.4、4.2和4.3 mRNA 与蛋白表达。结果心衰组家兔左室 K_v 通道α亚单位 K_v 1.4、4.2和4.3 mRNA(目的基因/GAPDH 分别为0.48±0.09,0.37±0.07,0.42±0.11)和蛋白(目的蛋白/β-actin 分别为0.33±0.09,0.22±0.07,0.29±0.11)表达显著低于假手术组(目的基因/GAPDH 分别为0.85±0.08,0.66±0.07,0.67±0.08;目的蛋白/β-actin 分别为0.68±0.13,0.53±0.15,0.49±0.10),P 均<0.01;而辛伐他汀组(目的基因/GAPDH 分别为0.77±0.10,0.50±0.10,0.57±0.12;目的蛋白/β-actin 分别为0.58±0.10,0.36±0.10,0.43±0.12)显著高于心衰组,P 均<0.01。结论辛伐他汀能够防止心衰家兔左室瞬间外向钾通道表达的下调。

Objective To investigate the effects of simvastatin on the left ventricular （LV） expression of transient outward potassium channel in rabbits with experimental heart failure （ HF ）. Methods HF model was established by ligating the left anterior descending coronary artery of rabbits. Rabbits were randomized into simvastatin group （ HF ＋ S, 10mg·kg^-1·d^-1 for 10 weeks, n = 8）, HF group （n = 9 ）, and sham group （n = 9 ）. Left ventricular remodeling and function were evaluated by echocardiography and hemodynamic measurements 10 weeks after operation. The mRNA and protein expressions of K, 1.4 , K,4.2 and K,4.3 potassium channel ot subunit in LV were determined by semiquantitative RT-PCR and Western blot. Results Simvastatin attenuated LV remodeling and improved cardiac function. The mRNA and protein expressions of Kv1. 4, K,4. 2 and Kv4. 3 potassium channel ot subunit in HF rabbits （ 0. 48 ±0. 09,0. 37 ±0. 07,0. 42 ±0. 11 ; 0. 33 ±0. 09,0. 22 ±0. 07,0. 29 ±0. 11 ） were significantly decreased compared with sham rabbits （0. 85 ±0. 08 ,0. 66 ±0. 07,0. 67 ±0. 08;0. 68 ±0. 13 ,0. 53 ±0. 15 ,0. 49 ±0. 10, all P 〈 0. 01 ）, and these decreases could be attenuated by simvastatin （0. 77 ±0. 10,0. 50 ±0. 10,0. 57 ±0. 12;0. 58 ±0. 10,0. 36 ±0. 10,0. 43 ±0. 12, all P 〈0. 01 vs. HF）. Conclusion Simvastatin not only attenuated LV remodeling and improved LV function but also prevented the downregulation of LV transient outward potassium channel expressions in rabbits with experimental HF.