雷诺嗪通过抑制心室肌细胞低氧情况下增大的晚钠电流来减小反向Na+-Ca2+交换电流-生理学专业论文.docxVIP

万方数据 万方数据 武汉 武汉科技大学硕士学位论文 雷诺嗪通过抑制心室肌细胞低氧情况下增大的晚钠电 流来减小反向 Na+-Ca2+交换电流 摘要 雷诺嗪可抑制多种病理条件下的晚钠电流（INa.L），并作为新型的心血管治疗 药物，被临床用于治疗心绞痛，然而低氧增大的INa.L可否被雷诺嗪所抑制尚无报道。 本实验采用全细胞膜片钳技术探究了雷诺嗪在治疗浓度下（10 μM）对低氧增大 的INa.L和反向INCX的影响。结果表明，2 μM TTX和9 μM雷诺嗪均能明显抑制常氧 下心室肌细胞的INa.L和反向INCX，而正向INCX变化不明显。另外常氧下，当用2 μM TTX抑制了心室肌细胞的INa.L和反向INCX后，再在灌流液中加入9 μM雷诺嗪后，INa.L 和反向INCX未见进一步变化。雷诺嗪（3, 6, 9 μM）对低氧增大的INa.L和反向INCX呈 浓度依赖性抑制作用, 而对正向INCX无明显改变。另外两组实验采用不同的加药顺 序对INa.L和INCX进行干预。其一，用9μM雷诺嗪抑制了INa.L和反向INCX之后，再加入 2 μM TTX则INa.L和反向INCX无明显改变。而在另一组实验中，先加入2 μM TTX使 INa.L和反向INCX被明显抑制，而后再加入9 μM雷诺嗪，INa.L和反向INCX没有明显改 变。此外，在单项动作电位的记录中，低氧条件下产生的早期后除极可被9 μM雷 诺嗪所抑制。结论：雷诺嗪可通过抑制INa.L而使常氧下的反向INCX减小，还可浓度 依赖性抑制低氧增大的INa.L，进而使低氧增大的INa.L和反向INCX减小，并且抑制低 氧条件下出现的早期后除极。 关键词：低氧；雷诺嗪；INa.L；INCX；膜片钳 I Abstract Ranolazine（RAN）, a novel clinical antianginal agent, inhibits late sodium current （ INa.L ） under many pathological conditions, while it is unclear whether hypoxia-increased INa.L can be inhibited by RAN. In this study, whole-cell patch-clamp technique was used to explore the effects of RAN on hypoxia-increased INa.L and reverse Na+/Ca2+ exchange current（INCX）in therapeutic concentrations. The data show that INa.L and reverse INCX could be significantly reduced by 2 μM tetrodotoxin（TTX）or 9 μM RAN under normoxia, while the inward INCX changed very little . In addition, INa.L and reverse INCX were decreased obviously by 2 μM TTX, but no longer changed when 9 μM RAN was added into afterwards in normoxia. RAN（3, 6, and 9 μM）attenuated the increase of INa.L and reverse INCX in a concentration-dependent manner during hypoxia, while inward INCX remained unaffected throughout the study. In the other two separate experiments, the hypoxia-increased INa.L and reverse INCX were associated with different sequences of drug administration. One is that INa.L and reverse INCX were inhibited by 2 μM TTX, whereas no changes appeared with adding 9 μM RAN afterwards. In another group, INa.L and reverse INCX were decreased by 9 μM RAN, but no further chang