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

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,能剂量依赖地拮抗缺血再灌注所导致的大鼠心脏损伤。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。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。结果显示: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。以上表明: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。

Inhibitory effects of N-n-Butyl haloperidol iodide on L-type Ca2＋ current induced by hypoxia/reoxygenation in rat cardiomyocytes

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 cur- rents （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 concentra tion-dependent manner,especially the outward current. Our study suggests that Fe can protect myocytes from H/R injury, which might be related to the inhibition of the inward and outward of INcx.