桔皮苷对糖尿病大鼠心电活动的影响

Effects of Hesperidin on cardiac electrophysiology of diabetic rats

目的研究桔皮苷对糖尿病模型大鼠心电活动的影响。方法30只SD大鼠随机分为三组。糖尿病模型组(n=12):一次性腹腔注射大剂量链脲佐菌素(STZ)诱导建立糖尿病模型;桔皮苷干预组(n=12):建立糖尿病模型,每日10 mg/kg桔皮苷灌胃;对照组(n=6):不建模亦不干预。分组处理4周后,记录和比较三组大鼠在体、离体心电图及心室肌细胞动作电位特征。以1×10^(-6) mol/L和5×10^(-6) mol/L桔皮苷灌流糖尿病模型组大鼠心室乳头肌,连续记录动作电位变化。结果在体心电图分析显示,与对照组比较,糖尿病模型组和桔皮苷干预组大鼠心率均明显加快(P<0.01,P<0.05);糖尿病模型组大鼠QT间期显著延长(P<0.05),桔皮苷干预组大鼠QT间期与对照组比较差异无统计学意义(P>0.05)。离体心电图观察发现,糖尿病模型组快速型心律失常发生率为75.0%,明显高于桔皮苷干预组的16.7%(P<0.05)。心室肌细胞动作电位各项参数比较显示,糖尿病模型组心肌细胞静息电位、动作电位幅度和0期最大除极速率均较对照组明显减小或下降,而动作电位时程延长;与糖尿病模型组比较,桔皮苷干预组动作电位各项参数则更接近对照组。两种浓度的桔皮苷灌流实验显示,与1×10^(-6) mol/L桔皮苷灌流比较,5×10^(-6) mol/L桔皮苷灌流对糖尿病大鼠心室乳头肌动作电位的恢复效应更为显著。结论桔皮苷可能通过逆转心电异常活动而降低糖尿病大鼠的心律失常发生率,且呈一定的浓度依赖效应。

Objective ： To investigate the effects of Hesperidin on cardiac electrophysiology of diabetic rats. Methods Thirty SD rats were randomly divided into three groups. Diabetic model group （ n = 12） ： diabetic model was induced by intraperitoneal injection of large amount of streptozotocin （STZ） ; Hesperidin intervention group （ n = 12） ： diabetic model was established, and were intragastrically administrated with 10 mg/kg Hesperidin daily; control group （ n = 6） ： without model establishment and intervention. After treatment for 4 weeks, in vivo and in vitro ECG and characteristics of action potentials of ventricular muscles were recorded and compared. Papillary muscles of ventricle of diabetic model group were perfused with 1 × 10^-6 mol/L or 5 × 10^-6 mol/L Hesperidin, and changes of action potentials were continuously recorded. Results In vivo ECG analysis revealed that the heart rates of diabetic model group and Hesperidin intervention group were much faster than that of control group （P 〈 0.01, P 〈 0.05）, QT interval of diabetic model group significantly prolonged （P 〈 0.05）, while there was no significant difference in QT interval between control group and Hesperidin intervention group （P 〉 0. 05）. In vitro ECG analysis indicated that the prevalence of tachyarrhythmia in diabetic model group was 75.0%, significantly higher than that of Hesperidin intervention group （ 16. 7%） （ P 〈 0.05）. Analysis of action potentials of ventricular muscles revealed that the resting membrane potential, amplitude of action potential and maximum upstroke velocity of phase 0 of diabetic model group were significantly lower than those of control group, while the action potential duration was longer than that of control group. Compared with diabetic model group, the parameters of action potentials in Hesperidin intervention group were more approximate with those of control group. Perfusion tests with two concentrations of Hesperidin demonstrated that 5 × 10^-6 mol/L Hesperidin perfusion performed better than 1 × 10^-6 mol/L Hesperidin perfusion in recovery of action potentials of papillary muscles of ventricle of diabetic rats. Conclusion Hesperidin may dose-dependently decrease the prevalence of arrhythmia by reversing the abnormal electrophysiological activities in diabetic rats.