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目的观察丹参酮ⅡA对腹主动脉缩窄高血压豚鼠心肌肥厚的作用,并在离子通道水平探讨其预防肥厚心肌心律失常可能的电生理机制。方法将豚鼠随机分为对照组、模型组和丹参酮组,每组15只,采用腹主动脉结扎技术建立高血压豚鼠模型。术后4周丹参酮组给予丹参酮[10mg/(kg.d)]干预治疗,腹腔注射,1次/d,共用8周,其余两组给予等量生理盐水腹腔注射。用尾动脉测压仪测量豚鼠尾动脉收缩压,超声心动图检测舒张末期室间隔厚度(IVSTd)和舒张末期左心室后壁厚度(LVPWTd),计算左心室质量指数(LVMI),应用标准的全细胞膜片钳技术记录各实验组心肌细胞膜上膜电容、动作电位时间(APD)及电压依赖性钾通道中快激活成分(Ikr)和慢激活成分(Iks)电流密度的变化。结果与对照组相比,模型组血压升高,LVMI、LVPWTd和IVSTd明显增加[LVMI(2.10±0.09)比(1.55±0.04)mg/g,LVPWTd(2.17±0.11)比(1.64±0.12)mm,IVSTd(1.89±0.04)比(1.51±0.08)mm,均P<0.01);与模型组相比,丹参酮组心肌细胞APD缩短,膜电容降低,Ikr、Iks电流密度降低[APD50(16.1±2.9)比(68.4±2.8),膜电容(270±15)比(370±17),Ikr(2.49±0.24)比(3.18±0.25),Iks(10.10±1.11)比(13.79±0.20),均P<0.01]。结论丹参酮ⅡA在抗心肌肥厚的同时能明显阻断肥厚心肌细胞出现异常增大的Ikr和Iks离子流,缩短肥厚心肌细胞APD,降低膜电容。
Objective To observe the effect of tanshinone Ⅱ A on the hypertrophy of hypertensive guinea pigs with abdominal aorta and to explore its possible electrophysiological mechanism at the level of ion channels for prevention of cardiac arrhythmia. Methods Guinea pigs were randomly divided into control group, model group and tanshinone group, with 15 rats in each group. Hypertensive guinea pig model was established by abdominal aortic ligation. The tanshinone group was given tanshinone [10mg / (kg · d)] for 4 weeks after operation, and was injected intraperitoneally for 1 week for 8 weeks. The other two groups were injected intraperitoneally with the same volume of saline. The caudal arterial pressure was used to measure the contractile pressure of guinea pig tail artery. The left ventricular posterior wall thickness (LVPWTd) and the left ventricular posterior wall thickness (LVMI) were measured by echocardiography. The left ventricular mass index (LVMI) Cell patch clamp technique was used to record the change of membrane capacitance, action potential time (APD) and current density of Ikr and Iks in the voltage-dependent potassium channel in each experimental group. Results Compared with the control group, the blood pressure increased and the LVMI, LVPWTd and IVSTd significantly increased in the model group [LVMI (2.10 ± 0.09) vs (1.55 ± 0.04) mg / g and LVPWTd (2.17 ± 0.11) (P <0.01). Compared with the model group, the APD of tanshinone group was decreased, the membrane capacitance was decreased and the current density of Ikr and Iks was decreased [APD50 (16.1 ± 2.9) ) Ratio (68.4 ± 2.8), membrane capacitance (270 ± 15), (370 ± 17), Ikr (2.49 ± 0.24), (3.18 ± 0.25) and Iks (10.10 ± 1.11) <0.01]. Conclusion Tanshinone ⅡA can obviously block the abnormally increased Ikr and Iks ion currents in hypertrophic cardiomyocytes, shorten the APD of hypertrophic cardiomyocytes and decrease the membrane capacitance.