白藜芦醇上调心肌缝隙连接蛋白43的表达降低大鼠心肌梗死后心律失常

Resveratrol exerts anti-arrhythmic effects in rats with myocardial infarction through up-regulation of cardiac connexin43 expression

目的：探讨白藜芦醇对大鼠心肌梗死（ MI）后室性心律失常的影响。方法将造模成功的心肌梗死SD大鼠随机分为心肌梗死组（MI组，n＝8）和白藜芦醇组（Res组，n＝8），另设假手术组（Sham组，n＝8），其中Res组给予10 mg· kg－1· d－1剂量的灌胃（1次／d），MI组和sham组给予5％羧甲基纤维素钠灌胃。4周后，对大鼠行在体程序性电生理刺激实验；Masson ’ s染色观察心肌梗死面积变化；免疫组织化学法检测心肌缝隙连接蛋白43（connexin43，Cx43）和 Cx43的368位丝氨酸磷酸化（P368Cx43）分布水平；免疫印迹法检测心肌 Cx43、P368Cx43和蛋白激酶 Cβ2（PKCβ2）表达水平。结果与MI组相比，白藜芦醇能显著降低室性心律失常的诱发率（87．5％对37．5％，P＜0．05），增加心室颤动（室颤）阈值[（3．2±0．3）V对（5．2±0．8）V，P＜0．05]；与sham组相比，MI组的Cx43表达量显著降低（P＜0．05），然而P368Cx43和PKCβ2的表达量却显著升高（P＜0．05）。白藜芦醇能明显增加梗死心肌Cx43表达量（P＜0．05），降低P368Cx43表达和PKCβ2表达（P＜0．05）。结论白藜芦醇能有效改善大鼠MI心肌电生理学特性，提高心肌Cx43表达，减少室性心律失常的发生率。

Objective To investigate effect of resveratrol on ventricular arrhythmias in rats with myo-cardial infarction .Methods Twenty-four adult male Sprague-Dawley rats were randomly divided into myocar-dial infarction group（MI group,n=8）, resveratrol group （Res group,n=8） after successful establishment of MI model,and sham group （n=8） which underwent thoracotomy and pericardiotomy without the left anterior descending ligation.Res group was given a dose of 10 mg· kg-1· d-1 resveratrol （i.g.once a day） for 4 weeks. MI group and sham group received 5%sodium carboxymethyl cellulose gavage .At 4 weeks after induced MI the programmed electrical stimulation was performed in vivo electrophysiological studies .Myocardial infarct size was detected by Masson’s staining.The distribution of connexin43（Cx43） and P368Cx43 were detected by immuno-histochemical staining methods .The Cx43,P368Cx43 and PKCβ2 expressions were measured using western blot . Results Compared with MI group ,resveratrol significantly reduced the incidence rate of induced ventricular arrhythmias （87.5%vs.37.5%,P〈0.05）,and the ventricular fibrillation threshold was significantly higher [（3.2±0.3）V vs.（5.2±0.8）V,P〈0.05].Compared with the sham group,the expression of Cx43 within the infracted myocardium was significantly lower （P〈0.05）,while the expressions of P368Cx43 and PKCβ2 were greatly higher （ P〈0.05 ） .Cx43 levels increased in myocardial infarction rats which received resveratrol （ P〈0.05）.Conclusion Resveratrol could effectively improve the cardiac electrophysiological properties in MI rats and increase myocardial expression of Cx 43 protein, and could prevent the occurrence of ventricular arrhythmias.