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作 者:王秀秀 邹丽 钱薇 顾有为 李立明 许正新[1,2,3,4] WANG Xiuxiu;ZOU Li;QIAN Wei;GU Youwei;LI Liming;XU Zhengxin(Department of Pharmacology,School of Medicine,Yangzhou University,Yangzhou 225000,China;Jiangsu Key Laboratory of Animal Infectious Diseases and Zoonosis Prevention and Control,Yangzhou 225001,China;Key Laboratory of Integrative Medicine Prevention and Treatment in Jiangsu Province,Yangzhou 225001,China;Jiangsu Key Laboratory of Non-coding RNA Basic and Clinical Transformation,Yangzhou 225009,China)
机构地区:[1]扬州大学医学院药理教研室,江苏扬州225000 [2]江苏省重点动物传染病和人畜共患病预防控制共创中心,江苏扬州225001 [3]江苏省中西医结合老年病防治重点实验室,江苏扬州225001 [4]江苏省非编码RNA基础与临床转化重点实验室,江苏扬州225009
出 处:《中国现代应用药学》2019年第18期2256-2261,共6页Chinese Journal of Modern Applied Pharmacy
基 金:扬州大学大学生科研创新计划项目(X20180729)
摘 要:目的研究荭草苷(orientin,Ori)对大鼠心室肌细胞钠通道电流(INa)的影响,探讨Ori在离子通道层面的抗心律失常机制。方法使用Langendorff恒温恒压灌流装置、单酶解消化法分离大鼠心室肌细胞,应用全细胞膜片钳技术记录、观察不同浓度Ori作用前后大鼠心室肌细胞钠通道电流(INa)的变化。结果低于2μmol·L^-1的Ori对INa无明显影响,3,10,30μmol·L^-1的Ori使INa的I-V曲线显著上移,峰值钠电流(INa-Peak)由给药前的(-81.49±3.9)pA/pF依次变为(-74.38±4.1)pA/pF,(-63.05±2.8)pA/pF和(-55.35±3.2)pA/pF;Ori使激活曲线右移、失活曲线左移,失活后恢复曲线显著右移,最大半数激活电位(V1/2-ac)由给药前的(-53.66±4.12)mV分别变为(-44.64±1.9)mV,(-38.95±1.7)mV和(-30.21±1.5)mV;最大半数失活电位(V1/2-in)由给药前的(-51.68±0.76)mV分别变为(-60.17±1.5)mV,(-68.51±1.4)mV和(-75.22±1.37)mV,恢复时间(τ)由给药前的(18.38±0.84)ms分别变为(24.53±1.4)ms,(35.25±1.3)ms和(68.75±1.58)ms。结论Ori能浓度依赖性抑制大鼠心室肌细胞的INa,并能显著影响其激活、失活及失活后恢复的动力学特征。OBJECTIVE To study the effects of orientin(Ori)on the sodium channel currents(INa)of ventricular myocardial cells in rats,and to explore its anti-arrhythmic mechanisms at the ion channel level.METHODS Ventricular myocardial cells were enzymatically isolated from rats by Langendorff with constant pressure and temperature.The whole-cell patch clamp techniques were used to observe the changes of INa at different concentrations of Ori.RESULTS There was no significant effect on INa,when the concentration of Ori was<2μmol·L^-1.I-V curve of INa significantly moved up under the influence of 3,10 and 30μmol·L^-1 Ori,and the peak sodium current(INa-Peak)was reduced from(-81.49±3.9)pA/pF to(-74.38±4.1)pA/pF,(-63.05±2.8)pA/pF and(-55.35±3.2)pA/pF.Ori moved the steady-state activation curve of INa to the right,the steady-state inactivation curve to the left,and the recovery curve to the right.The half activation voltage(V1/2-ac)changed from(-53.66±4.12)mV to(-44.64±1.9)mV,(-38.95±1.7)mV and(-30.21±1.5)mV.The half inactivation voltage(V1/2-in)changed from(-51.68±0.76)mV to(-60.17±1.5)mV,(-68.51±1.4)mV and(-75.22±1.37)mV.And the recovery time(τ)changed from(18.38±0.84)ms to(24.53±1.4)ms,(35.25±1.3)ms and(68.75±1.58)ms.CONCLUSION Ori block INa of rat ventricular myocytes in a concentration-dependent manner.It also has a significant effect on the kinetics characteristics of activation,inactivation and the recovery.
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