目的 研究多西环素对离体大鼠心肌缺血再灌注后心律失常易感性的影响,并通过分析缝隙连接的重新分布探讨其可能机制.方法 48只大鼠随机分为空白对照组、缺血再灌组、多西环素干预组.采用Langendorff灌注系统,制备离体大鼠缺血再灌注模型,用ELISA方法检测各组间大鼠心肌基质金属蛋白酶-9(MMP-9)的含量,通过Western-blot方法及免疫荧光标记方法检测心肌Cx43的分布及含量.用电生理方法观察多西环素对缺血再灌注后室性快速性心律失常发生的影响.结果 缺血再灌组及多西环素干预组较空白对照组MMP-9水平显著增高(P<0.001).多西环素干预组较缺血再灌组MMP-9水平显著降低(P<0.001).多西环素干预组再灌注后自发性室速的发生率有所减低、室性快速性心律失常诱发率显著降低(P<0.05).多西环素能够显著减轻缺血再灌注引起的Cx43侧化分布,但Cx43的数量没有显著改变(P>0.05).结论 多西环素可通过减少MMP-9的表达,减轻缺血后缝隙连接的侧化分布并减少再灌注心律失常发生.%Aim To investigate the effects and the possible mechanisms of doxycycline on the susceptibility of ventricular tachyarrhythmias in isolated ischemia-reperfusion rat hearts. Methods 48 isolated rat hearts perfused with a langendorff instrument were divided into blank group,ischemia-reperfusion group and doxycycline intervention group( n = 16 , respectively ). Matrix metalloproteinase-9( MMP-9 )were detected hy ELISA. Cx43 in the cardiomyocytes were quantified by western-blotting and localized by immunofluorescence. The risk of inducible ventricular tachyarrhythmias was evaluated by electrophysiological study. Results Doxycycline could significantly dilute MMP-9 in the ischemia-reperfusion rat hearts( P ＜ 0. 001 ). Ventricular tachyarrhythmias tended to he reduced in doxycycline-perfused hearts( P ＜ 0. 05 ). Redistrihution of Cx43 can he ohserved in the tissue of doxycycline-perfused hearts. Conclusion Doxycycline can prevent gap junction redistrihution hy reducing MMP-9 in the heart tissue, thereby decrease inducihle ventricular tachyarrhythmias in ischemia-reperfusion hearts.
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