Objective To investigate the mRNA expression level of the HCN channel subtypes in sinoatrial node of adult SD rats with volume-overloaded heart failure as well as the effects of bisoprolol on this process and heart rate. Methods Healthy male SD two-month-old rats were selected to establish the abdominal ateriovenous fistula as a left-to-right shunt model in order to induce volume-overload heart failure; sham operated rats served as controls. After the rats were fed together for 2 months, they were randomly administered with placebo or bisoprolol.Echocardiography was performed four weeks later to record intrinsic heart rate and hemodynamic changes. Then the total RNA was extracted and the mRNA expression level of HCN channel subtypes was determined by RT-PCR. Results Two months after the modeling, echocardiography showed that the heart size enlarged, thickness of the left ventricle increased significantly, and ejection fraction lowered significantly in the operation group (P<0.01). Four-week bisoprolol treatment failed to reverse heart dilation caused by aorta level left-to-right shunt (P>0.05), but improved the heart function (P<0.05) and elevated intrinsic heart rate (P<0.01). The outcomes of real-time RT-PCR showed that ① In the sham group, the mRNA expression of HCN2 channel was predominant (79%) compared with that of HCN4 channel (21%); ② The relative expression level of HCN4 mRNA decreased significantly in placebo group compared with that in sham group (0.09±0. 02 vs. 1.04±0.13, P<0.01), but that of HCN2 mRNA did not differ significantly among the 3 groups; 3) After intervention with bisoprolol, the expression level of HCN4 mRNA elevated markedly (0. 99±0. 15 vs. 0.09±0.02, P<0.01). Conclusion Bisoprolol can decrease base heart rate and increase intrinsic heart rate as well as improving the heart function of heart failure rats. The expression of HCN4 mRNA in sinoatrial node of left-to-right shunt rats is deceased and restored to almost normal level by bisoprolol, which may be one of the possible mechanisms of affecting intrinsic heart rate and improving the heart function.%目的 以大动脉水平左向右分流SD大鼠心衰模型为研究对象,观察固有心率、窦房结起搏电流HCN2及HCN4亚型mRNA在心脏重构过程中的变化,以及选择性β1-受体阻滞剂比索洛尔对它们的影响.方法 通过腹腔动静脉造瘘术建立慢性大动脉水平左向右分流心力衰竭模型,并以假手术组动物为对照.共同饲养2月后,随机分别给予安慰剂或比索洛尔.4周后再次行超声心动检查；测定血流动力学改变及固有心率；提取RNA进行实时定量RT-PCR测定各组HCN通道各亚型mRNA的表达水平.结果 造模后2月,超声心动图显示,手术组大鼠心脏扩大,左室厚度显著增高,射血分数则显著降低(P＜0.01).比索洛尔干预4周后未能逆转大动脉水平左向右分流引起的心腔扩大(P＞0.05),但可改善心脏功能(P＜0.05)并提高固有心率(P＜0.01).HCN通道蛋白mRNA检测显示:①大鼠实房结组织中HCN2表达占优势,HCN4相对较少(79％、21％);②安慰剂组HCN4 mRNA水平较假手术组明显下降(0.09±0.02 vs.1.04±0.13,P＜0.01),而HCN2 mRNA表达在各组间没有统计学差异；③比索洛尔治疗后,HCN4基因mRNA水平明显回升(0.99±0.15 vs.0.09±0.02,P＜0.01).结论 ①比索洛尔干预在改善心衰大鼠心脏功能的同时,可以降低基础心率、升高固有心率；②大动脉水平左向右分流导致心衰大鼠窦房结HCN4通道mRNA的表达降低,比索洛尔治疗可以逆转该通道的重构.这是其影响固有心率、改善心功能的可能机制.
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