乌司他丁对大鼠心肌缺血再灌注早期Toll样受体4表达的影响  

Effects of ulinastatin on expression of Toll-like receptor 4 during early myocardial ischemia/reperfusion in rats

作　　者：许崇恩[1] 王公明[2] 张孟元[2] 王旭[2] 邹承伟[1] 徐艳冰[2] 

机构地区：[1]山东大学附属省立医院心外科,济南市250021 [2]山东大学附属省立医院麻醉科,济南市250021

出　　处：《中华麻醉学杂志》2012年第11期1390-1392,共3页Chinese Journal of Anesthesiology

基　　金：山东省科技攻关项目（2008GG30002042）

摘　　要：目的探讨乌司他丁对大鼠心肌缺血再灌注早期心肌Toll样受体4（TLR4）表达的影响。方法健康成年sD大鼠30只，体重250～280g，雌雄不拘，采用随机数字表法，将大鼠随机分为3组（n=10）：假手术组（S组）、缺血再灌注组（I／R组）和乌司他丁组（U组）。采用结扎左冠状动脉前降支30min后再灌注的方法制备大鼠心肌缺血再灌注模型。U组于心肌再灌注前5min静脉内注射乌司他丁1×10^4IU／kg，S组及I／R组给予等量生理盐水。再灌注5h时处死大鼠，取缺血区心肌组织，观察心肌病理学结果；采用TUNEL法测定大鼠心肌细胞凋亡情况，计算凋亡指数；采用免疫组化法测定心肌TLR4的表达水平，采用ELIAS法测定TNF-α的含量。结果与S组比较，I／R组及U组心肌细胞凋亡指数、心肌TLR4表达水平和TNF-α含量升高（P〈0．05）；与I／R组比较，UTI组心肌细胞凋亡指数、心肌TLR4表达水平和TNF—α含量降低（P〈0．05），UTI组心肌病理学损伤较I／R组减轻。结论乌司他丁减轻大鼠心肌缺血再灌注损伤的机制与抑制心肌再灌注早期TLR4的表达，减轻心肌炎性反应有关。Objective To investigate the effects of ulinastatin on the expression of Toll-like receptor 4 （TLR4） during myocardial ischemia/reperfusion （I/R） in rats and the possible mechanism. Methods Thirty adult Sprague-Dawley rats, weighing 250-280 g, were randomly divided into 3 groups （ n = 10 each） ： sham operation group （group S）, I/R group and ulinastatin group （group U）. Myocardial ischemia was induced by 30 rain occlu- sion of left anterior descending coronary artery followed by repeffusion. Ulinastatin 1 × 10^4 IU/kg was injected intra- venously at 5 rain before reperfusion in group U, while the equal volmne of normal saline was given in groups S and I/R. The animals were sacrificed at 5 h of reperfusion and myocardial specimens were obtained for microscopic ex- amination and determination of myocardial apoptosis （using TUNEL）, TLR4 expression （by immuno-histochemis- try） and TNF-α content （by ELIAS）. The apoptotic index was calculated. Results Compared with S group, the apoptotic index, TLR4 expression and TNF-α content were significantly increased in groups 1/R and U （P 〈 0.05） . Compared with I/R group, the apoptotic index, TLR4 expression and TNF-a content were significantly de- creased （ P 〈 0.05）, and the pathological changes were significantly reduced in group U. Conclusion The mech- anism by which ulinastatin alleviates myocardial I/R injury is related to inhibition of TLR4 expression and reduction of inflammatory responses during early I/R in rats.

关 键 词：胰蛋白酶抑制剂 TOLL样受体4 心肌再灌注损伤 

分 类 号：R54[医药卫生—心血管疾病] R614[医药卫生—内科学]