替罗非班对急性心肌梗死再灌注模型猪的梗死区微血管的保护作用

摘要

目的 研究替罗非班对猪急性心肌梗死(AMI)再灌注后梗死区微血管血流的作用,探讨替罗非班减少AMI再灌注后梗死区微血管梗阻(microvessel obstruction,MO)的作用机制和与炎性因子的关系. 方法 中国实验用小型猪,随机分为对照组和替罗非班组.通过介入球囊封闭冠状动脉的方法堵闭左前降支中段90 min后,撤出球囊制作急性心肌梗死再灌注模型.采用延迟增强多层螺旋CT(delayed enhancement multi-slice spiral CT,DE-MSCT)检测心肌梗死面积并计算体积和梗死区微血管梗阻的情况,采用酶联免疫吸附法测定血清白细胞介素( IL)-6、IL-10浓度.最后处死小猪,取得心脏标本行2,3,5-氯化三苯基四氮唑(TTC)染色. 结果 对照组10只、替罗非班组9只实验猪成功穿刺并行冠状动脉造影.对照组和替罗非班组各6只猪的心肌梗死再灌注模型制作成功,对照组4只、替罗非班组3只实验小猪在DE-MSCT上出现心肌梗死区微血管梗阻.两组微血管梗阻体积在AMI再灌注后各时间点均呈增加趋势,替罗非班组微血管梗阻体积在再灌注后1、24、48、72 h均小于对照组,分别为(9.6±3.1)％与(4.8±0.7)％、(13.4±3.3)％与(5.8±1.2)％、(15.1±3.8)％与(6.4±1.2)％和(15.9±4.6)％与(6.6±0.8)％,差异有统计学意义(t值分别为6.99、13.76、14.21和11.38,均P＜0.05)；两组在AMI后30 min时,血清IL-6、IL-10水平开始升高,AMI再灌注后10 min至72 h的各时间点,替罗非班组血清IL-6水平明显低于对照组,而血清IL-10水平高于对照组,差异均有统计学意义(P＜0.05或P＜0.01). 结论 替罗非班可缩小AMI再灌注后心肌梗死区微血管梗阻范围,除抗血小板机制外其还可能与减轻AMI再灌注后炎症反应有关.%Objective To investigate the effects of tirofiban on microvascular flow in infarction zone after coronary reperfusion in pigs with acute myocardial infarction (AMI),and to explore its mechanism of decreasing microvessel obstruction (MO) and the relationship with inflammatory factors. Methods Chinese mini pigs were randomized into control group and tirofiban treatment group.Acute myocardial infarction was induced by balloon occluding the medium segment of the left anterior descending artery for 90 min,and then reperfusion was created by withdrawing the balloon.The infarct myocardium and MO area were detected with delayed enhancement multi-slice spiral CT (DE-MSCT),the serum levels of IL-6 and IL-10 were measured with enzyme linked immunosorbent assay (ELISA).The pigs were killed, the heart were excised and stained with 2, 3, 5-triphenyltetrazolium chloride (TTC). Results 6 pig models were successfully established in each group.4 pigs in control group and 3 pigs in tirofiban treating group experienced MO.The MO volume was increased at every time after reperfusion in both groups,while the MO volume was significantly reduced in tirofiban treatment group compared with control group at 1 h [(9.6 ± 3.1) ％ vs.(4.8 ±0.7)％],24 h[(13.4±3.3) ％ vs.(5.8±-1.2)％],48 h[(15.1±3.8)％ vs.(6.4±1.2)％] and 72 h [(15.9±4.6) ％ vs.(6.6±0.8)％ after reperfusion (t=6.99,13.76,14.21,11.38,all P＜0.05).Compared with the baseline,the levels of serum IL-6 and IL-10 in both groups were increased at 30 min after AMI.In tirofiban treatment group,the level of serum IL-6 was significantly lower and serum IL-10 was higher than those in control group (P＜0.05 and P＜0.01) from 10 min to 72 h after reperfusion. Conclusions Tirofiban may lessen the MO area in infarction zone of AMI after reperfusion,which may be ascribed to its anti-inflammation besides anti-platelets.