伊伐布雷定在急性心房颤动中的作用

发布时间：2018-04-18 01:34

本文选题：犬 + 急性心房颤动　；参考：《西南医科大学》2017年硕士论文

【摘要】：目的:研究犬急性房颤模型中HCN通道亚单位(HCN2和HCN4)基因和蛋白表达及超级化激活电流(If)的变化在致电重构后对急性房颤发生的影响。探讨HCN通道特异性阻滞剂-伊伐布雷定对抑制急性房颤发生及维持的作用。方法:将18只犬随机分为三组,空白对照组(n=6),刺激组(n=6),刺激+伊伐布雷定组(n=6)。空白对照组仅行电极标测记录;刺激组给予快速起搏心房6h;刺激+伊伐布雷定组给以6h快速心房起搏过程中持续静脉泵入伊伐布雷定(0.5mg/kg/h),成功建模后检测三组犬心率及心脏电生理的变化,取心脏不同部位样本(左右心房及左右心耳),采用Real-time PCR检测三组HCN2及HCN4 m RNA的表达变化,Western-blotting检测HCN2及HCN4的蛋白含量,全细胞膜片钳技术检测单个心房肌细胞上If的改变。结果:空白对照组犬心率不随时间的推移而改变,刺激组心率随实验时间推移而升高,刺激+伊伐布雷定组心率随实验时间推移下降,三组差异有统计学意义(P0.01)。经6小时快速心房起搏后,刺激组房颤诱发率及房颤持续的时间较对照组均明显升高,房颤诱发率为46.67%vs.14.67%,(P0.01),房颤持续时间为700±309.84s vs.120±58.99s,(P0.01)。而刺激+伊伐布雷定组的房颤诱发率及房颤持续时间则回将至8.67%及105±51.67s,其差异与刺激组相比有统计学意义(P0.01)。对照组有效不应期随时间改变无明显变化,刺激组有效不应期随起搏时间时间明显进行性缩短,差异有统计学意义(p0.01)。相反,刺激+伊伐布雷定组有效不应期随时间进行性延长,与刺激组对比,差别有统计学意义(p0.01)。在心房不同部位,与对照组相比,刺激组左心房(la)、右心房(ra)、左心耳(laa)、右心耳(raa)内hcn2和hcn4通道的mrna表达水平增加,差异具有统计学意义(p0.01)。与刺激组相比,刺激+伊伐布雷定组左心房(la)、右心房(ra)、左心耳(laa)、右心耳(raa)内hcn2和hcn4通道的mrna表达降低,差异具有统计学意义(p0.01)。同样刺激组相对于对照组左心房(la)、右心房(ra)、左心耳(laa)、右心耳(raa)内hcn2和hcn4通道的蛋白含量表达增加,差异具有统计学意义(p0.01)。与刺激组相比,刺激+伊伐布雷定组左心房(la)、右心房(ra)、左心耳(laa)、右心耳(raa)内hcn2和hcn4通道的蛋白含量表达降低,差异具有统计学意义(p0.01)。在全细胞的if电流记录时显示,刺激组犬心房肌细胞的if电流比对照组if电流明显增大(5.19±0.60pa/pfvs2.68±0.30pa/pf,p0.01),与刺激组相比,给予伊伐布雷定后的犬心房肌细胞电流明显减小至2.17±0.63pa/pf,p0.01。提示hcn通道功能活动与表达在用药后发生抑制变化。结论:1.急性房颤发生时,hcn通道基因和蛋白表达上调,if电流增大。2.伊伐布雷定可以降低心率,延长心房有效不应期,降低房颤诱发率,缩短房颤持续时间。3.伊伐布雷定可以通过抑制HCN2和HCN4通道表达,减小If电流来抑制心房组织电重构,从而抑制急性房颤的发生。
[Abstract]:Aim: to investigate the effects of HCN channel subunits (HCN2 and HCN4) on the occurrence of acute atrial fibrillation (AAF) in canine acute atrial fibrillation (AAF) model.To investigate the effect of HCN channel specific blocker (Evasbradide) on inhibiting the occurrence and maintenance of acute atrial fibrillation (AAF).Methods: eighteen dogs were randomly divided into three groups: control group (n = 6), stimulation group (n = 6) and ivalburetine group (n = 6).The blank control group was only recorded by electrode mapping.The stimulation group was given rapid atrial pacing for 6 hours, and the Ifabradine group was given continuous intravenous infusion of 0.5 mg / kg 路kg / h of ivalburetine during 6 h rapid atrial pacing. The heart rate and cardiac electrophysiology of the three groups were measured after successful modeling.The expression changes of HCN2 and HCN4 m RNA in three groups were detected by Real-time PCR. The protein contents of HCN2 and HCN4 were detected by Western-blotting, and the changes of if on single atrial myocytes were detected by whole-cell patch clamp technique.Results: the heart rate of the blank control group did not change with the passage of time, but the heart rate of the stimulation group increased with the passage of experimental time, and the heart rate of the Evalburetine group decreased with the passage of the experimental time. The difference among the three groups was statistically significant (P 0.01).After 6 hours of rapid atrial pacing, the atrial fibrillation evoked rate and the duration of atrial fibrillation in the stimulation group were significantly higher than those in the control group. The atrial fibrillation evoked rate was 46.67 vs.14.67p0.01g, and the duration of atrial fibrillation was 700 卤309.84s vs.120 卤58.99s (P 0.01).The rate of atrial fibrillation induced and the duration of atrial fibrillation in the treatment group were 8.67% and 105 卤51.67 s respectively, and the difference was statistically significant compared with the stimulation group (P 0.01).In the control group, the effective refractory period did not change significantly with time, while in the stimulation group, the effective refractory period was significantly shortened with the pacing time, and the difference was statistically significant (p 0.01).On the contrary, the effective refractory period of Ifabradine group was prolonged progressively with time, compared with the stimulation group, the difference was statistically significant (p 0.01).Compared with the control group, the mrna expression levels of hcn2 and hcn4 channels in the stimulation group were significantly higher than those in the control group (P < 0.01), and the expression levels of hcn2 and hcn4 channels in the stimulation group were significantly higher than those in the control group (P < 0.01), and the expression levels of mrna and hcn4 channels in the stimulation group were significantly higher than those in the control group (P < 0.01).Compared with the stimulation group, the mrna expression of hcn2 and hcn4 channels in the Ifabradine group was significantly lower than that in the control group (P < 0.01).The protein expression of hcn2 and hcn4 channels in the same stimulation group was significantly higher than that in the control group (P 0.01).Compared with the stimulation group, the protein expression of hcn2 and hcn4 channels in the left atrium, right atrium, left atrial Aura, right atrial auricle and right atrial auricle were decreased in the treatment group, and the difference was statistically significant (P 0.01).The if current recorded in the whole cell showed that the if current in the stimulation group was significantly higher than that in the control group (5.19 卤0.30PA / pffp0.01g). Compared with the stimulation group, the current of the canine atrial myocytes treated with ivalburetine was significantly decreased to 2.17 卤0.63pa-pfp0.01.The results suggest that the function and expression of hcn channel are inhibited after medication.Conclusion 1.During the occurrence of acute atrial fibrillation, the gene and protein expression of HCN channel upregulated the if current. 2. 2.Ifabradine can reduce heart rate, prolong atrial effective refractory period, reduce atrial fibrillation induced rate, and shorten atrial fibrillation duration by 3. 3.Ifabradine can inhibit the electrical remodeling of atrial tissue by inhibiting the expression of HCN2 and HCN4 channels and decreasing the if current, thus inhibiting the occurrence of acute atrial fibrillation.
【学位授予单位】：西南医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R541.75

【参考文献】