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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大鼠窦房结组织中HCN2表达占优势,HCN4相对较少(79%、21%);②安慰剂组HCN4mRNA水平较假手术组明显下降(0.09±0.02 vs.1.04±0.13,P<0.01),而HCN2mRNA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。
Objective To study the changes of intrinsic heart rate, sinoatrial pacemaker current HCN2 and HCN4 subtypes mRNA during cardiac remodeling, and the effect of selective β1-receptor The effect of the blocker bisoprolol on them. Methods Chronic left ventricular shunt was established by intraperitoneal arteriovenous ostomy in rats. The sham operation group was used as control. After 2 months of co-feeding, they were randomized to placebo or bisoprolol. Four weeks later, echocardiography was performed again. The hemodynamic changes and intrinsic heart rate were measured. RNA was extracted for real-time quantitative RT-PCR to detect the mRNA expression of HCN channels in each group. Results In February after modeling, echocardiography showed that in the operation group, heart enlargement, left ventricular thickness increased significantly and ejection fraction decreased significantly (P <0.01). After 4 weeks of bisoprolol intervention, heart chamber enlargement (P <0.05) failed to reverse left aortic shunting (P <0.05), but cardiac function (P <0.05) and heart rate increased (P <0.01). The mRNA expression of HCN channel showed that: (1) The expression of HCN2 in the sinus node was predominant in rats, with relatively fewer HCN4 (79%, 21%); ② The HCN4 mRNA level in placebo group was significantly lower than that in sham operation group (0.09 ± 0.02 vs. 1.04 ± 0.13, P <0.01), while the expression of HCN2 mRNA had no statistical difference among the three groups; ③ After bisoprolol treatment, the mRNA level of HCN4 increased significantly (0.99 ± 0.15 vs.0.09 ± 0.02, P <0.01). Conclusion Bisoprolol intervention can improve the heart function of heart failure rats, reduce the basic heart rate and increase the intrinsic heart rate. ② The level of aorta left-right shunt decreases the expression of HCN4 channel mRNA in sino-atrial node of heart failure rats, Lolotherapy reverses the remodeling of this pathway. This is its possible mechanism of affecting the intrinsic heart rate and improving cardiac function.