辛伐他汀对血脂正常兔心肌缺血再灌注后L型钙电流的影响

目的通过研究辛伐他汀预处理对兔心肌缺血再灌注后L型钙离子通道电流(ICa-L)的影响,探讨他汀类药物抗心律失常的细胞学离子机制。方法45只新西兰大耳白兔随机分为3组:缺血再灌注组(I-R组,结扎冠状动脉左前降支30min后再开放120min);辛伐他汀治疗组(他汀组,手术前给予辛伐他汀5mg·kg-1·d-1,3天);假手术对照组(对照组,只开胸不结扎血管)。观察心律失常发生情况。采用酶解法分离缺血部位心室肌外膜单个心室肌细胞,采用全细胞膜片钳技术,记录ICa-L,同时检测各组血脂水平。结果各组动物血脂水平无显著差异。I-R组心律失常发生率较对照组增加,他汀组较I-R组心律失常发生率明显下降。对照组、I-R组和他汀组ICa-L电流密度峰值(0mV)分别为-3.13±1.22pA/pF(n=16),-4.24±0.92pA/pF(n=15)和-3.46±0.85pA/pF(n=13)。I-R组较对照组明显升高(P<0.05),他汀组较I-R组明显下降(P<0.05),他汀组与对照组无差异(P>0.05)。结论缺血再灌注可导致梗死区心室肌细胞I明显增加,辛伐他汀预处理可逆转这种变化。

Effects of simvastatin on L-type calcium current in ventricular myocytes of normocholesterolemic rabbits suffering from ischemia and reperfusion

Objective To investigate the effects of simvastatin on L-type calcium current (ICa-L)in left ventricular myocytes of rabbit heart undergoing ischemia-reperfusion,so as to explore the cellular(ionic ) basis of statin treatment for antiarrhythmia. Metheds Forty-five rabbits were randomly divided into three groups: ischemic-reperfusion group (I-R), simvastatin intervention group(Statin group) and sham-opreted control group(CON group). Anesthetized rabbits were subjected to 30-min ischemia by ligation of the left anterior descending coronary artery and 60-min reperfusion after administration of oral simvastatin 5 mg·kg-1·d-1(Statin group) or placebo (I-R group) for 3 days.Single ventricular myocytes were isolated enzymatically from the epicardial zone of the infracted region derived from the hearts in I-R, Statin group and thesame anatomy region in CON .Whole cell patch clamp technique was used to record ICa-L. Simultaneously,the level of serum cholesterol was examined. Results There was no significant difference in serum cholesterol concentration among three groups. The peak ICa-L current density(at 0 mV) was significantly increased in I-R (-4.24±0.92 pA/pF,n=15) compared with CON (-3.13±1.22 pA/pF, n= 16) and Statin (-3.46±0.85 pA/pF, n= 13) group,while the peak ICa-L current density in Statin group was not different from CON group( P>0.05). Conclusions It is implied that ischemia-reperfusion induces significant up-regulation of ICa-L,and pretreatment with simvastatin could attenuate these changes.