水蛭素对大鼠急性心肌梗死后室性心律失常的影响

Effects of Hirudin on Ventricular Arrhythmia after Acute Myocardial Infarction in Rats

【目的】探讨凝血酶的直接抑制剂重组双功能水蛭素对大鼠急性心肌梗死后室性心律失常的影响及相关机制。【方法】将70只雄性SD大鼠随机分为10组:水蛭素(HIR)结扎前(HIR0min)组,HIR结扎后5min(HIR5min)组,HIR结扎后10min(HIR10min)组,HIR结扎后20min(HIR20min)组,HIR结扎后30min(HIR30min)组),和生理盐水(NS)对应的各时间组,即NS0min,NS5min,NS10min,NS20min,NS30min,最终每组7只。观察各组室性心律失常的发生情况,Evans法计量各组心梗面积及采用逆转录聚合酶链反应对各组缺血心肌组织的IP3R家族的三种亚型进行测定。【结果】水蛭素组发生室性心律失常的持续时间及心律失常评分较生理盐水组在结扎后5～20min均减少(P<0.05);IP3R家族的三种亚型均与心梗后室性心律失常持续时间呈正相关性;但IP3R2mRNA在结扎后10min及IP3R3mRNA在结扎后10min和20min,HIR组较NS组下调(P<0.05)。【结论】水蛭素有抗心梗后室性心律失常的发生作用,其机制可能为通过IP3R2和IP3R3实现的,而并非IP3R1。

【Objective】 To determine the effects and possible mechanism of the thrombin antagonist r-RGD-Hirudin（HIR） on ventricular arrhythmia （VA） after acute myocardial infarction （AMI）.【Methods】 Seventy adult male Sprague-Dawley rats were randomly subjected to the 10 groups according to duration of left coronary occlusion： HIR 0 min,HIR 5 min,HIR 10 min,HIR 20 min,HIR 30 min,and normal saline（NS） 0 min,NS 5 min,NS 10 min,NS 20 min,NS 30 min;and the average of every group is 7 rats.Acute myocardial infarction was produced by the occlusion of the left anterior descending coronary artery,then the measurements of arrhythmia and infarction sizing by Evans blue were assessed as well as the expression of three isoforms of inositol 1,4,5-trisphosphate receptors （IP3Rs） mRNA in ischemic myocardium by reverse transcriptase polymerase chain reactions （RT-PCR ）.【Results】 Compared with NS groups,the measurements of VA in HIR were reduced significantly in 5 to 20 minutes after AMI （P 0.05）.The incidence of VA was all positive related to the expression of three isoforms of IP3Rs mRNA （P 0.01）.Compared with NS groups,the expression of type2,inositol 1,4,5-trisphosphate receptor （IP3R2） mRNA at 10 min and type3,inositol 1,4,5-trisphosphate receptor mRNA （IP3R3） at 10 min and 20 min after AMI were significant decreased （P 0.05） in HIR groups.【Conclusion】 The thrombin antagonist r-RGD-Hirudin exerts its myocardial protection against ventricular arrhythmia after acute myocardial infarction possible through IP3R2 and IP3R3 and not type1,inositol 1,4,5-trisphosphate receptor （IP3R1）.