丙泊酚及其孪药159P抗室性心律失常作用初探  

Preliminary Study on Anti-Ventricular Arrhythmia Effect of Propofol and Its Twin-Drug 159P

作　　者：余银 林开斌 李帅 张雪 朱董飞 方圆 郭祖奉 许涛[1] 曾步兵[4] 黄冬[1] YU Yin;LIN Kaibin;LI Shuai;ZHANG Xue;ZHU Dongfei;FANG Yuan;GUO Zufeng;XU Tao;ZENG Bubing;HUANG Dong(Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China;Zhongshan Hospital of Fudan University,Shanghai 200025,China;Institute of Life Sciences,Chongqing Medical University,Chongqing 400016,China;School of Pharmacy,East China University of Science and Technology,Shanghai 200025,China)

机构地区：[1]上海交通大学医学院附属第六人民医院,上海200025 [2]复旦大学医学院附属中山医院,上海200025 [3]重庆医科大学生命科学研究院,重庆400016 [4]华东理工大学药学院,上海200025

出　　处：《心血管病学进展》2024年第10期942-947,共6页Advances in Cardiovascular Diseases

基　　金：国家自然科学基金(82172068);上海交通大学医学院双百人计划——研究型医师(SBR2022204)。

摘　　要：目的初步探究丙泊酚及其孪药159P的抗室性心律失常作用。方法临床研究纳入10例拟接受导管消融术的特发性室性心律失常患者,手术前均接受低剂量(1 mg/kg)丙泊酚,评估丙泊酚抗室性心律失常作用。动物实验将40只SD大鼠随机分为空白对照组(Control)、氯化钡干预组(BaCl 2)、美托洛尔干预组(BaCl 2+metoprolol)、丙泊酚干预组(BaCl 2+propofol)、丙泊酚孪药159P干预组(BaCl 2+159P)。药物预处理后经大鼠股静脉快速推注氯化钡(25 mg/kg)诱发心律失常,持续记录Ⅱ导联心电图,记录各组大鼠室性心动过速发生率和死亡率,统计分析15 min内心电图RR、PR、QT间期以及QRS波群等心电图参数变化。采用苏木精-伊红染色观察各组心脏毒性发生情况,免疫组织化学染色评估间隙连接蛋白43(Cx43)的表达水平。结果临床研究证明了丙泊酚抗心律失常的有效性,且来源于右心室流出道的特发性室性心律失常对丙泊酚表现出更高的敏感性。动物实验结果显示丙泊酚及其孪药159P均显著降低氯化钡诱导大鼠室性心动过速的发生率和死亡率。心电图参数分析表明丙泊酚及其孪药159P抑制了氯化钡引起的RR、PR和QT间期延长,维持心电活动稳定。相较于美托洛尔,二者心动过缓发生率更低。心脏组织学显示丙泊酚及其孪药159P不会引起心律失常大鼠心脏组织学改变。免疫组织化学染色显示丙泊酚及其孪药159P上调了心肌组织Cx43的表达水平。结论丙泊酚及其孪药159P可能通过调控Cx43发挥抗室性心律失常作用,且显示出较好的安全性。Objective To investigate the anti-ventricular arrhythmia effect of propofol and its twin-drug 159P.Methods Ten patients with idiopathic ventricular arrhythmia who were to undergo catheter ablation were enrolled in the clinical study and received a low dose(1 mg/kg)of propofol prior to the procedure to assess the anti-ventricular arrhythmic effects of propofol.Animal experiments were performed by randomly dividing 40 SD rats into the blank control group(Control),the barium chloride group(BaCl 2),the metoprolol intervention group(BaCl 2+metoprolol),the propofol intervention group(BaCl 2+propofol),and the propofol twin-drug 159P intervention group(BaCl 2+159P).After drug pretreatment,barium chloride(25 mg/kg)was rapidly injected through the femoral vein of rats to induce arrhythmia,and theⅡ-lead electrocardiogram was continuously recorded to observe the incidence of ventricular tachycardia and mortality of rats in each group,and to statistically analyze the changes of the electrocardiogram parameters,such as RR,PR,QRS,and QT intervals within 15 min.Hematoxylin-eosin staining was used to observe the occurrence of cardiotoxicity in each group and immunohistochemical staining was used to assess the expression level of connexin 43(Cx43).Results Clinical studies demonstrated the antiarrhythmic efficacy of propofol and idiopathic ventricular arrhythmia originating from the right ventricular outflow tract showed higher sensitivity to propofol.Animal studies showed that propofol and its twin-drug 159P significantly reduced the incidence and mortality of barium chloride-induced ventricular tachycardia in rats.Analysis of electrocardiographic parameters showed that propofol and its twin-drug 159P reversed barium chloride-induced prolongation of RR,PR and QT intervals and maintained stable cardiac activity.Both had a lower incidence of bradycardia side effects compared to metoprolol.Cardiac histology showed that propofol and 159P did not induce histological changes in the hearts of arrhythmic rats,and Cx43 staining showed th

关 键 词：丙泊酚 丙泊酚孪药 室性心律失常 

分 类 号：R965[医药卫生—药理学]