辛伐他汀心肌保护作用的新机制：对心肌细胞钠氢交换的抑制作用初探

目的：探讨辛伐他汀是否通过抑制心肌细胞的钠氢交换保护心肌急性氧化损伤.方法：用可标记pH值的荧光探针SNARF-1和可标记Ca2＋的荧光探针Huo-3/AM同时负载原代培养的乳鼠心肌细胞30 min,先后加入H2O2及辛伐他汀等药物,激光共聚焦显微镜检测,根据荧光探针被激发出的不同颜色的荧光强度,同步绘出细胞内pH值（pHi）和细胞内钙离子浓度（Ca2＋]i）的变化趋势图.结果：辛伐他汀使H2O2引起的pHi和Ca2＋]i上升分别下降0.08±2.28和0.16±0.53（P ＜0.05）,与阿米洛利（EIPA）的作用相似.结论：辛伐他汀能通过影响心肌细胞内的钠氢交换快速起效,使细胞内pH值下降,抑制钙超载,从而对心肌的氧化损伤起急性保护功能.

Cardioprotective effect of simvastatin: new insights into inhibition of Na + -H + exchange in cardiomyocytes

Objective：To determine the protective effects of simvastatin on cardiomyocyte acute oxidative injury via inhibition of Na ＋ -H ＋ exchange （NHE）. Methods： Primary cultured cardiomyoeytes of neonatal rats were loaded with both luminescent probes SNARF-1 for labeling pH value and Fluo-3/AM for labeling Ca2＋ for 30 minutes, and were subjected to laser eonfocal microscopic examination after adding hydrogen peroxide followed by simvastatin. The figures representing the trends of variation in intracdlular pH （pHi） and Ca2 ＋ （ Ca2 ＋ ]i） were plotted simultaneously, based on the intensity of various colors emitted by luminescent probes. Results ： As of similar effect of amiloride （ EIPA）, the increase in phi and Ca2 ~ ] i, induced by hydrogen peroxide, was reduced by （0.08 ± 2.28 ） and （0.16±0.53 ） as a result of blockade by simvastatin （ P 〈 0.05 ）, respectively. Conclusion： Simvastatin exhibits cardioprotective effects of acute cardiomyocyte oxidative injury via exerting influence on NHE in a rapid manner, leading to reduction in intracellular pH value and inhibition of calcium overload.