腺苷对猪急性心肌梗死再灌注后内皮素-1的影响

Effect of Adenosine on Endothelin-1 in the Infarcted Reflow and No-reflow Myocardium of Mini-Swines

目的评价急性心肌梗死(AMI)再灌注后内皮素-1(ET-1)的变化及腺苷对ET-1的影响,探讨无再流的可能机制。方法中华小型猪24只,随机分成对照组、腺苷组和假手术组,每组8只。冠状动脉结扎3h,松解1h制备AMI再灌注模型。采用放射免疫方法测定AMI前5min、AMI后5min、AMI后180min和再灌注后5min和60min血浆ET-1的含量及正常、缺血、无再流区心肌组织ET-1的变化;逆转录-聚合酶链反应的方法观察正常、缺血和无再流区心肌组织ET-1mRNA的表达。结果与AMI前比较,对照组和腺苷组AMI后5min、AMI后180min、再灌注后5min和60min的血清ET-1水平均显著升高(P<0·01),且呈递增趋势(P<0·01)。腺苷组除AMI前外,各时间点的血浆ET-1水平均显著低于对照组(P<0·05,P<0·01)。与正常区心肌组织比较,对照组和腺苷组缺血区和无再流区心肌组织ET-1含量均显著升高(P<0·01),且无再流区ET-1含量升高比缺血区更显著(P<0·01)。与对照组比较,腺苷组仅缺血区心肌组织ET-1含量显著降低(P<0·01)。与正常区心肌组织比较,对照组和腺苷组缺血区心肌组织ET-1的mRNA表达均显著上调(P<0·01),而无再流区心肌组织ET-1的mRNA表达均显著下降(P<0·01)。与对照组比较,腺苷组仅在缺血区ET-1的mRNA表达显著降低(P<0·01)。结论内皮细胞受损可能是无再流发生的重要机制之一,腺苷可能通过保护内皮细胞起到减少无再流的作用。

Objective To evaluate the effect of adenosine on endothelin-1 （ ET-1 ） after acute myocardial infarction （AMI） and reperfusion and explore the possible mechanism of no-reflow. Methods Twentyfour mini-swines were randomized into three study groups： control group （ n = 8 ）, adenosine treated group （ n = 8 ）, and sham-operated group （ n = 8 ）. The mini-swines in the groups were subjected to 3 hours of coronary occlusion, followed by 60 minutes of reperfusion except those in the sham-operated group. The levels of ET-1 in blood sample, normal, infracted reflow and no-reflow myocardium were evaluated by radioimmunoassay （RIA）. The gene expressions of ET-1 in normal, infracted reflow and no-reflow myocardium were quantiffed by reverse transcription-polymerase chain reaction. Results In both control group and adenosine group, compared with that at the baseline, ET-1 in blood sample significantly increased at 5 minutes and 180 minutes of left anterior descending coronary artery occlusion, as well as 5 and 60 minutes of reperfusion （ all P 〈 0. 01 ）. In adenosine group, the levels of ET-1 were significantly lower than those in the control group （ P 〈 0. 05, P 〈0. 01 ）. In both control group and adenosine group, compared with that in normal myocardium, ET-1 levels in both infarcted reflow and no-reflow myocardium significantly increased （ both P 〈 0. 01 1 in no-reflow myocardium significantly higher than that in infarcted reflow myocardium sine group, the level of ET-1 in infarcted reflow myocardium was significantly lower ）, with the level of ET- （P 〈 0. 01 ）. In adenothan that in the control group （P 〈 0. 01 ）. In both control and adenosine groups, compared with that in normal myocardium, the gene expression of ET-1 in infarcted reflow myocardium was significantly up-regulated （P 〈 0. 01 ）, while that of ET-1 in. no-reflow myocardium significantly down-regulated （ P 〈 0. 01 ）. In adenosine group, the level of ET-1 in infarcted reflow myocardium was significantly lower than that in the control group （P 〈0. 01 ）. Conclusion The endothelium injury may be one of the important mechanisms for no-reflow phenomenon. Adenosine cay prevent endothelium from injury to reduce no-reflow.