碘化N-正丁基氟哌啶醇对大鼠缺氧复氧心肌细胞钠钙交换体电流的抑制作用
黄勇攀1, 2，高分飞2，石刚刚2
（1 贵阳医学院药理学教研室，贵阳 550004；2 汕头大学医学院药理学教研室，广东汕头 515041）
摘要：碘化N-正丁基氟哌啶醇（N-n-butyl haloperidol iodide，F2）为本研究室改造合成的新化合物，前期研究发现F2 作为 L-型钙通道拮抗剂剂量依赖地拮抗缺血再灌注所致大鼠心脏损伤。目的：研究F2 对缺氧复氧（hypoxia/reoxygenation，H/R）大鼠心肌细胞钠钙交换体电流的作用并探讨其保护机制。方法：采用Langendorff 灌流系统灌流SD 大鼠心脏，标准酶解法消化分离得到单个心室肌细胞。正常台式液灌流5min，立即灌流充90%N2-10%CO2的缺氧液, 建立体外心肌细胞H/R 模型，采用全细胞膜片钳技术记录对照、模型以及不同浓度F2（0.1，1，10μmol/L）对心肌细胞钠钙交换体电流，观察H/R 状态F2 对心肌细胞钠钙交换体电流的影响。结果：缺氧抑制钠钙交换体电流，主要是抑制外向电流；H/R 引起钠钙交换体电流增大，尤其是外向电流的增大。F2 呈浓度依赖地抑制钠钙交换体电流，钠钙交换体电流I-V 曲线上移。结论：F2 能抑制钠钙交换体电流，尤其是外向电流，防止H/R 时心肌细胞的钙超载，保护心肌细胞。
关键词：碘化N-正丁基氟哌啶醇；全细胞膜片钳；缺氧复氧；钠钙交换体电流
中图分类号：R966 文献标志码：A
Inhibitory effects of N-n-Butyl haloperidol iodide on L-type Ca2+ current induced by hypoxia/reoxygenation in rat
cardiomyocytes
Huang Yongpan1, 2, Gao Fenfei2, Shi Ganggang2
(1 Department of Pharmacology, Guiyang Medical University, Guiyang 550004, China;2 Department of Pharmacology, Medical College, Shantou University, Shantou Guangdong 515041, China)
Abstract: The study was designed to investigate the effects of N-n-butyl haloperidol iodide (F2) on sodium/calcium exchanger currents (NCX) including outward and inward currents during hypoxia/reoxygenation (H/R) in rat ventricular myocytes. Single ventricular cells were obtained by enzymatic dissociation. In whole-cell patch-clamp studies, the NCX outward and inward currents (INCX) were recorded from isolated rat ventricular myocytes. Results show that hypoxia inhibited the INCX, especially the outward current. H/R enhanced the amplitude of INCX obviously, especially the outward current. F2 inhibited INCX in a concentration-dependent manner，especially the outward current. Our study suggests that F2 can protect myocytes from H/R injury, which might be related to the inhibition f the inward and outward of INCX.
Keywords: N-n-butyl haloperidol iodide; whole-cell patch-clamp techniques; hypoxia/reoxygenation;
NCX outward and inward currents