通心络对猪急性心肌梗死再灌注后内皮素-1的影响

Effect of Tongxinluo on Endothelin-1 in the Mini-Swine Model of Acute Myocardial Infarction and Reperfusion

目的评价急性心肌梗死(acute myocardial infarction,AMI)再灌注后内皮素-1(endothelin-1,ET-1)的变化及通心络对其影响,探讨无再流的可能机制。方法中华小型猪40只,随机分成模型组,小、中和大剂量通心络治疗组和假手术组,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(RIA)测定造模前、后和再灌注后血清及AMI再灌注后心肌组织ET-1含量;逆转录-聚合酶链反应(RT-PCR)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(1)与造模前比较,模型组造模后5min时、造模后3h、再灌注5min和1h的血ET-1水平显著升高,且呈递增趋势(均P<0·01)。而ET-1升高幅度中、大剂量通心络组均低于模型组(P<0·05,P<0·01)。(2)与正常区心肌组织比较,模型组和3个通心络组一样,缺血区和无再流区心肌组织中ET-1含量均显著升高(均P<0·01),且无再流区ET-1含量升高比缺血区更显著(均P<0·01)。与模型组比较,中和大剂量通心络组仅缺血区心肌组织中ET-1含量显著降低(P<0·01)。(3)与正常区心肌组织比较,模型组和通心络各组缺血区心肌组织中ET-1mRNA表达均显著上调(均P<0·01),而无再流区心肌组织ET-1mRNA表达均显著下降(均P<0·01)。与模型组比较,中和大剂量通心络组仅缺血区ET-1mRNA表达上调幅度显著降低(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,通心络可能通过保护内皮细胞起到了减少无再流的作用。

Objective To evaluate the change of endothelin-1 （ET-1） in the mini-swine model of acute myocardial infarction （AMI） and reperfusion and the effect of Tongxinluo （TXL） on it, and to explore the possible mechanism of no-reflow. Methods Forty mini-swines were randomized into 5 groups： the model group, the small,middle and large dose of TXL groups and the sham-operated group, 8 in each group. The AMI reperfusion model was established by coronary ligation for 3 hrs followed with relaxation for 1 hr. Plasma ET-1 content before and after AMI, and after reperfusion was determined respectively by radioimmunoassay. The ET-1 mRNA expression in myocardial tissue of normal, ischemic and no-reflow area were respectively quantified by reverse transcription-polymerase chain reaction. Results （1） Compared with before AMI, levels of plasma ET-1 at the time points of 5 min and 3 hrs after AMI, 5 min and 1 hrs after reperfusion in the model group were significantly raised, showing an increasing tendency （all P 〈0.01 ）. But the increment in the middle and large dose of TXL groups were all lower than that in the model group （P〈0.05）. （2） In the model and the TXL groups, levels of ET-1 in myocardial tissue of ischemic and no-reflow area were significantly higher than those in the normal area, and the increment in no-reflow area was higher than that in ischemic area （all P 〈0.01）. Compared with the model group, significant lowering of ET-1 in ischemic area was only shown in the middle and large dose of TXL groups （P〈0.01）. （3） In the model and the TXL groups, ET-1 mRNA expression in ischemic area was significantly higher （all P〈0.01）, while it in no-reflow area was significantly lower than that in the normal area respectively （all P 〈 0.01）. The raised ET-1 mRNA expression in the middle and large dose TXL groups was significantly lowered when compared with that in the model group （P 〈 0.01）. Conclusion The endothelium injury might be one of the important mechanisms for no-reflow phenomenon. TXL might reduce the no-reflow by protecting endothelium cells.