摘要
背景:阿片类药物可调控心肌细胞膜电位和Ca^(2+)电流的变化,但是目前二乙酰吗啡是否诱导心肌节律、细胞动作电位和钙离子电流改变尚未见报道。目的:探讨二乙酰吗啡对离体SD乳鼠心肌细胞动作电位和钙离子电流的影响。方法:(1)体外培养SD乳鼠心肌细胞,采用5个浓度二乙酰吗啡(0,10^(-2),10^(-3),10^(-4),10^(-5)mol/L)和20 mol/L维拉帕米作用于心肌细胞;(2)将细胞分为对照组、二乙酰吗啡组、二乙酰吗啡+维拉帕米组。后2组分别以二乙酰吗啡、二乙酰吗啡+维拉帕米(浓度20μmol/L)联合干预心肌细胞;对照组加入等量PBS。实验于2018-05-21经新疆医科大学第一附属医院动物实验医学伦理委员会批准,批准号IACUC201805-K1。结果与结论:(1)当不同浓度二乙酰吗啡干预心肌细胞24 h后,心肌细胞形态异常数量亦随其浓度的改变而明显增加,呈剂量依赖性改变。当二乙酰吗啡浓度逐渐升高,细胞存活数量亦逐渐减少,细胞胞质体积缩小,胞膜收缩,伪足减少,细胞核结构模糊。(2)与对照组相比,当加入二乙酰吗啡干预心肌细胞后,心肌细胞自发性搏动频率和节律差异有显著性意义。静息膜电位负值降低,动作电位中动作电位时程显著增加,动作电位幅度显著减小。(3)与对照组相比,二乙酰吗啡组中心肌膜电位改变数量明显增加,当加入维拉帕米后,心肌膜电位改变细胞数量有所降低。与对照组相比,心肌膜电位改变细胞数量有所升高。(4)提示二乙酰吗啡可致离体SD乳鼠心肌细胞形态异常,心肌自发性搏动频率和节律显著增加,心肌细胞膜电位和动作电位发生改变,钙通道阻滞剂维拉帕米对二乙酰吗啡引起的心肌细胞节律异常有一定改善作用。
BACKGROUND:Opioids can regulate the changes of membrane potential and Ca2+current in cardiomyocytes,but whether diacetylmorphine can induce the changes of cardiac rhythm,cell action potential and Ca2+current has not been reported.OBJECTIVE:To explore the effect of diacetylmorphine on action potential and calcium current of isolated cardiomyocytes from neonatal Sprague-Dawley rats.METHODS:Five concentrations of diacetylmorphine(0,10-2,10-3,10-4,10-5 mol/L)and 20 mol/L verapamil were used to treat the cardiomyocytes of neonatal Sprague-Dawley rats cultured in vitro.The cells were divided into control group,diacetylmorphine group,diacetylmorphine+verapamil group.The latter two groups were treated with diacetylmorphine and diacetylmorphine+verapamil(20μmol/L),respectively,while the control group was treated with the same amount of PBS.The study protocol was approved by the Animal Ethics Committee of the First Affiliated Hospital of Xinjiang Medical University on May 21,2018 with approval No.IACUC201805-K1.RESULTS AND CONCLUSION:At 24 hours of culture with different concentrations of diacetylmorphine,the number of cardiomyocytes with abnormal morphology increased significantly in a dose-dependent manner.When the concentration of diacetylmorphine increased,the number of survived cells decreased,with a reduction in the size of cytoplasm and number of pseudopods,the cell membrane was shrunk and the nuclear structure was blurred.Compared with the control group,when diacetylmorphine was added to intervene with the cardiomyocytes,there was a significant difference in the spontaneous beating frequency and rhythm of cardiomyocytes.The negative value of resting membrane potential decreased,while the time course of action potential increased significantly,and the amplitude of action potential decreased significantly.Compared with the control group,the number of cells with changes in the membrane potential significantly increased in the diacetylmorphine group.The addition of verapamil reduced the number of cells with changes in the membrane potential.Compared with the control group,the number of cells with variation of membrane potential was increased to some extents.These findings suggest that diacetylmorphine can induce cardiomyocyte morphological abnormality,increase the spontaneous beating frequency and rhythm of cardiomyocytes,and change the membrane potential and action potential of cardiomyocytes.Verapamil acts as a calcium channel blocker that can improve the rhythm abnormality of cardiomyocytes induced by diacetylmorphine.
作者
苏丽萍
刘丽
路子扬
苏天园
胡夏韵
蒲红伟
Su Liping;Liu Li;Lu Ziyang;Su Tianyuan;Hu Xiayun;Pu Hongwei(Department of Pathology,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830011,Xinjiang Uygur Autonomous Region,China;School of Basic Medicine,Xinjiang Medical University,Urumqi 830054,Xinjiang Uygur Autonomous Region,China;School of Public Health,Xinjiang Medical University,Urumqi 830054,Xinjiang Uygur Autonomous Region,China;Second Department of Thoracic Surgery,the First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,Shaanxi Province,China;Discipline Construction Section,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830011,Xinjiang Uygur Autonomous Region,China)
出处
《中国组织工程研究》
CAS
北大核心
2020年第26期4201-4207,共7页
Chinese Journal of Tissue Engineering Research
基金
新疆维吾尔自治区卫生计生委青年医学科技人才专项科研项目(WJWY-201827),项目负责人:苏丽萍。
