Apelin-13逆转布比卡因导致的心室肌细胞钠通道抑制:一项电生理研究  

Apelin-13 reversing bupivacaine-induced sodium channel blockade in rat ventricular myocytes:an electrophysiology study

作　　者：蔡茜茜[1] 刘乐[1] 南芙蓓 王权光[1] CAI Xixi;LIU Le;NAN Fubei;WANG Quanguang(Department of Anesthesiology,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,China)

机构地区：[1]温州医科大学附属第一医院麻醉科,325000

出　　处：《浙江医学》2025年第2期118-125,共8页Zhejiang Medical Journal

基　　金：国家自然科学基金项目(82200329);温州市基础性科研项目(Y2020161)。

摘　　要：目的探讨Apelin-13通过逆转心室肌细胞钠通道抑制解救布比卡因心脏毒性的机制。方法采用急性酶解法分离获得大鼠心室肌细胞。(1)将心室肌细胞分为Control组、Bup10组、Bup+Apln5组、Bup+Apln10组、Bup+Apln20组和Bup+Apln40组,Control组应用细胞外液灌流心室肌细胞,Bup10组分别以细胞外液和含布比卡因10μmol/L的细胞外液顺序灌流心室肌细胞,Bup+Apln5组、Bup+Apln10组、Bup+Apln20组和Bup+Apln40组以含布比卡因10μmol/L的细胞外液灌流后分别给予含5、10、20和40μmol/L Apelin-13的细胞外液灌流进行解救,测定动作电位、钠电流激活曲线、失活曲线和恢复曲线,并确定Apelin-13解救布比卡因钠通道阻滞的最佳浓度。(2)将心室肌细胞分为Bup组、Bup+Apln20组、Bup+F13A组、Bup+Chel组、Bup+Apln20+F13A组和Bup+Apln20+Chel组。其中,Bup组处理同Bup10组,Bup+Apln20组、Bup+F13A组和Bup+Chel组依次以含布比卡因10μmol/L和Apelin-1320μmol/L、F13A 3μmol/L和白屈菜红碱3μmol/L的细胞外液灌流心室肌细胞,Bup+Apln20+F13A组分别以含F13A 3μmol/L的细胞外液、含布比卡因10μmol/L+F13A 3μmol/L的细胞外液和含布比卡因10μmol/L+Apelin-1320μmol/L+F13A 3μmol/L的细胞外液顺序灌流心室肌细胞,而Bup+Apln20+Chel组则以白屈菜红碱3μmol/L替代F13A,其他处理相同。应用全细胞膜片钳技术测定心室肌细胞钠电流激活曲线、失活曲线和恢复曲线。结果与Control组比较,10μmol/L布比卡因可降低动作电位和钠电流峰值,正向移动激活G/G曲线和恢复曲线,负向移动失活I/I曲线。与布比卡因处理组比较,外源性Apelin-13(10、20和40μmol/L)处理可呈剂量依赖性地增加大鼠心室肌细胞钠电流峰值,负向移动激活G/G曲线和恢复曲线,正向移动失活I/I曲线。F13A或白屈菜红碱可显著消除20μmol/L Apelin-13对心室肌细胞钠通道的影响。结论Apelin-13逆转布比卡因导致的心室肌细胞钠离子通道激活、�Objective To elucidate the novel mechanism by which Apelin-13 rescues bupivacaine(Bup)cardiotoxicity by reversing sodium channel inhibition in ventricular myocytes.Methods The rat ventricular myocytes were isolated using acute enzymatic hydrolysis method.(1)Ventricular myocytes were divided into the Control,Bup10,Bup+Apln5,Bup+Apln10,Bup+Apln20,and Bup+Apln40 groups.The Control group used extracellular fluid to perfuse ventricular myocytes,while in Bup10 group,ventricular myocytes were perfused with extracellular fluid and the extracellular fluid containing 10μmol/L Bup successively.Bup+Apln5,Bup+Apln10,Bup+Apln20,and Bup+Apln40 groups were rescued by extracellular fluid perfusion which contained 10μmol/L Bup followed by perfusion with extracellular fluid containing 5,10,20,and 40μmol/L Apelin-13.The action potential,and sodium current activation,inactivation and recovery curves were measured,and the optimal concentration of Apelin-13 to rescue Bup-induced sodium channel blockade was determined.(2)Ventricular myocytes are divided into Bup,Bup+Apln20,Bup+F13A,Bup+chelerythrine(Chel),Bup+Apln20+F13A and Bup+Apln20+Chel groups.Among them,the Bup group was treated the same as Bup10 group,while the Bup+Apln20,Bup+F13A and Bup+Chel groups were in turn treated with ventricular myocytes perfusion by extracellular fluids containing Bup 10μmol/L,Apelin-1320μmol/L,F13A 3μmol/L and Chel 3μmol/L.In the Bup+Apln20+F13A group,ventricular myocytes were perfused with extracellular fluids containing F13A 3μmol/L,Bup 10μmol/L+F13A 3μmol/L,and Bup 10μmol/L+Apelin-1320μmol/L+F13A 3μmol/L successively,while in the Bup+Apln20+Chel group,the treatment was the same as the Bup+Apln20+F13A group except that Chel 3μmol/L was used instead of F13A.The sodium current activation,inactivation and recovery curves of ventricular myocytes were determined by whole-cell patch-clamp technique.Results Compared with the Control group,10μmol/L Bup could reduce the action potential and sodium peak current,positively shift the steady-activat

关 键 词：大鼠 心室肌细胞 布比卡因 APELIN-13 钠通道 

分 类 号：R54[医药卫生—心血管疾病]