替罗非班对大鼠心肌缺血再灌注后无复流及一氧化氮合酶活性和一氧化氮含量的影响

目的研究替罗非班对大鼠心肌缺血再灌注后无复流及一氧化氮合酶(NOS)活性、一氧化氮(NO)含量的影响,探讨替罗非班改善心肌缺血再灌注后无复流的作用机制。方法雄性Wistar大鼠,随机分为假手术组、对照组和替罗非班组。建立急性心肌缺血再灌注无复流模型,用硫黄素S活体染色,观察大鼠心肌无复流范围;伊文斯蓝、氯化三苯基四氮唑(TTC)染色评估大鼠心肌缺血及梗死范围;紫外分光光度计测定缺血再灌注120min时缺血区心肌内皮型一氧化氮合酶(eNOS)、诱导型一氧化氮合酶(iNOS)、总一氧化氮合酶(tNOS)活性及NO含量。结果缺血再灌注后120min,替罗非班组大鼠与对照组大鼠心肌缺血范围相似[(43.13±5.69)%比(39.98±3.75)%,P>0.05],但无复流范围及梗死范围明显小于对照组[(34.36±6.04)%比(52.09±6.89)%,P<0.01;(80.41±8.48)%比(90.13±5.72)%,P<0.05);对照组大鼠心肌的eNOS活性低于假手术组,iNOS、tNOS活性及NO含量高于假手术组(P<0.01);替罗非班组大鼠心肌的iNOS活性及NO含量高于假手术组(P<0.05,P<0.01),eNOS、tNOS活性与假手术组差异无统计学意义。与对照组比较,替罗非班组大鼠心肌的eNOS活性高于对照组(P<0.05),iNOS活性及NO含量低于对照组(P<0.05,P<0.01),tNOS活性较对照组有降低的趋势,但差异无统计学意义。结论大鼠心肌缺血90min再灌注120min可发生无复流现象;替罗非班可缩小无复流及梗死范围,其机制可能与保护内皮功能有关。

Effects of tirofiban on no-reflow phenomenon and endothelial function after myocardial ischemia/reperfusion in rats

Objective To investigate the effects of tirofiban on no-reflow phenomenon,nitric oxide synthase(NOS) activity and nitric oxide(NO) level after myocardial ischemia/reperfusion in rats.Methods Sixty male Wistar rats were randomized into sham operation group,control group and Tirofiban group.Control group and Tirofiban group were subjected to ischemia for 90 minutes by ligation of coronary artery and reperfusion for 120 minutes.No-reflow area(NRA) was evaluated by thioflavine S staining and risk area(RA) and infarct area(IA) were evaluated by Evans blue and Triphenyltetra zolium chloride(TTC) staining;endothelial NOS(eNOS),inducible NOS(iNOS) and total NOS(tNOS) activity and NO level in RA were detected by ultraviolet spectrophotometer.Results After 120 minutes of reperfusion,markedly reduced NRA and IA were observed in tirofiban group compared to control group [(34.36±6.04)% vs(52.09±6.89)%,P<0.01;(80.41±8.48)% vs(90.13±5.72)%,P<0.05];there was no statistical difference of RA between control group and tirofiban group[(43.13±5.69)% vs(39.98±3.75)%,P>0.05].Lower eNOS activity,higher iNOS and tNOS activity and higher NO level were detected in control group compared with sham operation group(all P<0.01).There were higher iNOS activity and NO level in tirofiban group than in sham operation group(P<0.05 and P<0.01 respectively);no statistical differences were found in eNOS and tNOS activity between tirofiban group and sham operation group.Compared to control group,eNOS activity was higher(P<0.05) while iNOS activity and NO level were lower(P<0.05 and P<0.01 respectively) in tirofiban group;a decreasing tendency(not significant) was observed in tNOS activity in tirofiban group.Conclusions Tirofiban may improve endothelial function by reducing NRA and IA after ischemia/reperfusion in rats.