替罗非班对大鼠心肌缺血再灌注后无复流及NF-κB激活的影响  

Effects of tirofiban on no-reflow and activation of NF-κB after myocardial ischemia/reperfusion in rats

作　　者：刘玲梅[1] 张梅[2] 刘艳红[3] 周欣[2] 叶帆[2] 何瑞波[4] 李玉明[2] 

机构地区：[1]天津市海河医院心脏科,天津300350 [2]中国人民武装警察部队医学院附属医院心血管病研究所 [3]天津市第三中心医院,天津300171 [4]中国人民武装警察部队医学院病理教研室,天津300162

出　　处：《中国病理生理杂志》2009年第10期1892-1897,共6页Chinese Journal of Pathophysiology

摘　　要：目的:研究血小板膜糖蛋白Ⅱb/Ⅲa受体拮抗剂替罗非班对大鼠心肌缺血再灌注后无复流及NF-κB激活的影响。方法:雄性Wistar大鼠,随机分为假手术组、心肌缺血再灌注组和替罗非班治疗组(60μg/kg,再灌注前30min股静脉注射)。心肌缺血再灌注组和替罗非班治疗组采用开胸冠状动脉结扎方法,缺血90min再灌注120min建立急性心肌缺血再灌注无复流模型。观察大鼠心肌缺血、梗死及无复流范围;免疫组织化学方法半定量分析心肌细胞及微动脉核因子-κBp65(NF-κBp65)的阳性表达;测定心肌髓过氧化物酶(MPO)活性及丙二醛(MDA)含量。结果:心肌缺血再灌注组和替罗非班治疗组大鼠缺血区心肌细胞及微动脉NF-κBp65的阳性表达、心肌MPO活性、MDA含量高于假手术组;替罗非班治疗组大鼠缺血区心肌细胞及微动脉NF-κBp65的阳性表达、心肌MPO活性、MDA含量低于心肌缺血再灌注组(P<0.05);心肌无复流范围及梗死范围小于心肌缺血再灌注组(34.36%±6.04%vs52.09%±6.89%,P<0.01;80.41%±8.48%vs90.13%±5.72%,P<0.05)。结论:大鼠心肌缺血90min再灌注120min时,可发生无复流现象;替罗非班可缩小心肌无复流及梗死范围,抑制NF-κB激活,减少中性粒细胞浸润及氧自由基释放。AIM： To investigate the effects of platelet glycoprotein Ⅱ b/Ⅲ a receptor inhibitor tirofiban on myocardial no - reflow and activation of NF - κB after acute ischemia/reperfusion in rats. METHODS ： Male Wistar rats were randomized into sham operation group, control group and tirofiban treatment group. Control group and tirofiban group were subjected ischemia for 90 min by ligation of coronary artery after thoracotomy and subsequently reperfusion for 120 min to establish acute myocardial ischemia/reperfusion no -reflow models. Thioflavine S, Evans blue and triphenyhetra zolium chloride （TIC） staining were performed to evaluate the area of no - reflow （ANR）, infracted area （IA） and risk area （RA） of the heart. Immunohistochemistry was used for semi - quantitative analysis of the expression of nuclear factor - κB 1965 （ NF - κB p65 ） protein in myocytes and arteriole. Activity of myeloperoxidase （MPO） and content of malondialdehyde （MDA） in risk area of the heart were detected by ultraviolet spectrophotometer. RESULTS： After 120 rain for reperfusion, compared to sham group, the statistical differences of higher positive expression of NF - κB p65 in myocytes and arteriole, activity of MPO and content of MDA both in control and tirofiban group were observed. Compared to control group, lower positive expression of NF - κB p65 in myocyte and arteriole, activity of MPO and content of MDA in tirofiban group were found （P 〈0. 05, P 〈0. 01 ）. A markedly reduced ANR and IA were observed in tirofiban group than those in control group （34.36% ±6.04% vs 52.09% ±6.89%, P〈0.01; 80.41% ±8.48% vs90. 13% ±5.72%, P〈0.05）. CONCLUSION： After myocardial ischemia/reperfusion for 120 min, no - reflow phenomenon can be observed in rats. Tirofiban reduces the areas of anatomic no - reflow and infarction, inhibits the activation of NF - κB in myocyte and arteriole, and decreases the infiltration of neutrophils and release of oxygen free radicals.

关 键 词：心肌再灌注损伤 无复流 血小板糖蛋白GP Ⅱb-Ⅲa复合物 NF—κB 替罗非班 

分 类 号：R541.4[医药卫生—心血管疾病]