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作 者:赵梅[1,2] 郭振丰 李天时[2] 徐博志 钱铭[2] 其力木格[2] 张莉[2] 洪远[2] 李雪连[2]
机构地区:[1]海南省第三人民医院药学部,海南三亚572000 [2]哈尔滨医科大学药学院药理学教研室,黑龙江哈尔滨150081
出 处:《中国医院药学杂志》2016年第17期1452-1455,共4页Chinese Journal of Hospital Pharmacy
基 金:国家自然科学基金项目(编号:81100134)
摘 要:目的:探究丹参酮ⅡA(TanshinoneⅡA)抗缺血性心律失常新机制。方法:采用结扎大鼠冠状动脉左前降支构建缺血性心律失常模型。实验分为正常对照组,心梗组,TanⅡA组。TanⅡA组每天给予20 mg·kg-1丹参酮ⅡA灌胃7 d后建立心梗模型,随后每日继续给予TanⅡA3个月。监测Ⅱ导联心电图,观察大鼠发生急性心肌梗死后,缺血性心律失常的发生率和死亡率;全细胞膜片钳技术记录各实验组心室肌细胞动作电位时程(APD)和瞬时外向钾电流Ito的变化情况;Western Blot检测各实验组钾通道蛋白Kv4.2的表达变化。结果:TanⅡA降低急性心梗所诱发的缺血性心律失常的发生率和死亡率。TanⅡA具有上调心梗诱发的缺血性心律失常心室肌细胞的Ito电流的作用。TanⅡA能够上调急性心梗诱发的缺血性心律失常大鼠心肌组织中Kv4.2蛋白的表达。结论:TanⅡA通过上调急性心肌梗死大鼠心肌中kv4.2蛋白的表达,恢复Ito电流,发挥了抗缺血性心律失常的作用。OBJECTIVE To explore new mechanism of tanshinone (Tan) ⅢA on arrhythmic rats. METHODS Acute myo- cardial infarction (MI) model in rats established by ligating left anterior descending coronary artery was used to induce ischemic arrhythmias. Rats were divided into three groups, normal control group, myocardial infarction group and Tan Ⅱ A group. TAN ⅡA (20 mg. kg^-1 ) was given daily, before MI (7 d) and after MI (3 months). Cardiac electrical activity was monitored by lead Ⅱ ECG. Whole-cell patch-clamp techniques were used to measure changes in cell action potential duration (APD) and transient outward potassium currents (Ito) in ventrieular myocytes isolated from rats. Kv 4. 2 level was analyzed by Western blot. RE- SULTS Incidence and mortality induced by MI were decreased by TAN ⅡA. TAN Ⅱ A recovered Ito current in ventricular myocytes of MI rat. Expression of Kv 4. 2 protein was upgraded by TAN ⅡA in ischemic arrhythmias rats. CONCLUSION TAN ⅡA upregulates expression of kv 4. 2 protein and recover Itg currents in MI rats.
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