丹参酮ⅡA对腹主动脉缩窄高血压豚鼠电生理异常的干预研究  

Effect of tanshinone Ⅱ A on electrophysiological abnormality of guinea pig model induced by abdominal aorta coarctation

作　　者：唐昱[1] 葛郁芝[2] 盛国太[1] 周裔忠[1] 曹乾嫱[1] 张繁之[1] 

机构地区：[1]江西省人民医院心内科,江西南昌330006 [2]江西省心血管病研究所

出　　处：《中华高血压杂志》2012年第4期378-382,共5页Chinese Journal of Hypertension

基　　金：江西省自然科学基金项目(2009GQY0060)

摘　　要：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 study the antiarrhythmic effect of tanshinone 11 A on the ventricular hypertrophy induced by abdominal aorta coarctation in guinea pigs. Methods Hypertrophic guinea pig model that made by abdominal aorta constriction were randomly divided into sham operation, cardiac hypertrophy and tanshinone treated group （ 15 in each group）. Tanshinone was given to guinea pigs in the tanshinone group starting from the 4 th week of experiment at dose of 10 mg/kg by peritoneal injection once a day for 8 weeks, while for rats in the other 2 groups, equivalent of normal saline was given instead. The systolic blood pressure （SBP） were measured. The end-diastolic interventricular septal thickness （IVSTd） and the left ventricular posterior wall thickness （LVPWTd） were detected by diasonography. The left ventricular mass index （LVMI） were calculated. The membrane capacity, action potential duration（APD） and Ikr, Iks density in cellular membrane of each group were observed by using patch clamp technique. Results The blood pressure, LVMI, LVPWTd and IVSTd in operation group were obviously higher than that in sham-operation group [（2.10±0.09）vs（1.55±0.04）mg/g, （2.17±0.11）vs （1.64±0.12）mm, （1.89±0.04）vs（1.51±0.08）ram, P〈0.01]. The membrane capacity and action potential duration were much higher in hypertrophic group [P〈0.01）. Compared with hypertrophic group, the prolongation of action potential duration was markedly shortened by tanshinone treatment, membrane capacity and peak amplitude of Ikr, Ik, were decreased [APD50 （16.1±2.9） vs （68.4±2.8）, MC（270±15） vs （370±17）, Ikr （2. 49±0. 24） VS （3. 18±0. 25）, Iks （10.10± 1.11） vs （13.79!0.20）, all P〈0.01]. Conclusions Tanshinone treatment could decrease the density of component of Iks and Iks in the hypertrophic eadiocyte, suggesting tanshinone can prevent the onset of antiarrhythmia.

关 键 词：丹参酮 心肌肥厚 电压依赖性钾通道 豚鼠 高血压 

分 类 号：R544.1[医药卫生—心血管疾病]