糖尿病大鼠心肌电学的改变及环维黄杨星D对其电生理的影响

Electrophysiological changes in rat ventricular myocardium of experimental diabetes and action of CVB-D

目的:观察糖尿病大鼠心肌电学变化特点,探讨环维黄杨星D(CVB-D)对糖尿病心肌电生理的影响。方法:以SD雄性大鼠尾静脉注射四氧嘧啶(alloxan,50mg.kg-1)复制糖尿病模型,选择以年龄相匹配的SD雄性大鼠作为对照组。2周后,记录大鼠体表心电图和右心室乳头肌跨膜电位,观察CVB-D对跨膜电位的影响。结果:糖尿病造模后第2周时,心率明显减慢于对照组,体表心电图QT间期和右室乳头肌动作电位时程(APD)各水平均明显长于对照组大鼠(P<0.01),而静息膜电位(RP)、动作电位幅度(APA)和超射值(OS)以及0期去极化最大速率(Vmax)均无明显变化。CVB-D具有剂量依赖效应,在13.3-63.3μmol.L-1范围内呈剂量依赖性地延长糖尿病大鼠和对照组大鼠APD30、APD50、APD70和APD90,对糖尿病大鼠APD延长作用更大。在33.3-63.3μmol.L-1浓度范围内,CVB-D呈剂量依赖性抑制糖尿病大鼠和对照组大鼠的静息电位(RP)、动作电位幅值(APA)和0期最大去极化速度(Vmax),但对糖尿病组抑制更大。研究结果还显示,CVB-D还具有时间依赖效应,当20μmol.L-1灌流心室肌10min后开始出现作用,对照组到40min左右作用达高峰,而糖尿病组40min后仍继续延长。结论:糖尿病大鼠右室乳头肌动作电位时程和QT间期明显延长。CVB-D可进一步延长糖尿病大鼠的APD,抑制其RP、APA、OS以及Vmax,作用较对照组明显。

AIM： To investigate the electrophysiological changes of diabetic myocardium and effects of cyclovirobuxine D （CVB- D） on its electrophysiology. METHODS： Diabetes was induced in male SD rats, using a single injection of alloxan into tail vein. Untreated age- matched animals were used as controls. Animal electrocardiogram （ECG） was recorded by 2 weeks. Effects of CVB- D on isolated right ventricular papillary muscle from experimental diabetic rats and control group were observed by recording the transmembrane potentials with conventional glass microelectrodes. RESULTS：QT intervals in ECG and action potential duration （APD） at all levels were significantly lengthened in myocardium from week 2 of diabetes. Within the concentration of 13.3 - 63.3 μmol· L-^-1, CVB - D prologated APD of diabetes in dose - dependent manner and more than that of control. Within the concentration of 33.3 - 63.3 μmol· L-^-1, CVB - D depressed RP, APA, Vmax and OS of diabetes in dose - dependent way and more than that of control. In addition, CVB - D at concentration of 20 μmol· L-^-1 prologated APD in a time - dependent manner. The most prologation of APD was attairved about 40 min in control, while more than 40 min in diabetes. CONCLUSION： The results show that QT intervals in ECG and APD at all levels are significantly lengthened in myocardium from week 2 of diabetes. CVB - D prolongates APD and inhibits RP, APA, OS and Vmax more in d. iabetes than in control.