CAJ | 학술논문

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～ 280 g,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30 min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5 min静脉内注射乌司他丁1×104 IU/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,UT1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.
목적 탐토오사타정대대서심기결혈재관주조기심기Toll양수체4(TLR4)표체적영향.방법 건강성년SD대서30지,체중250～ 280 g,자웅불구,채용수궤수자표법,장대서수궤분위3조(n=10):가수술조(S조)、결혈재관주조(I/R조)화오사타정조(U조).채용결찰좌관상동맥전강지30 min후재관주적방법제비대서심기결혈재관주모형.U조우심기재관주전5 min정맥내주사오사타정1×104 IU/kg,S조급I/R조급여등량생리염수.재관주5h시처사대서,취결혈구심기조직,관찰심기병이학결과；채용TUNEL법측정대서심기세포조망정황,계산조망지수；채용면역조화법측정심기TLR4적표체수평,채용ELIAS법측정TNF-α적함량.결과 여S조비교,I/R조급U조심기세포조망지수、심기TLR4표체수평화TNF-α함량승고(P＜0.05)；여I/R조비교,UT1조심기세포조망지수、심기TLR4표체수평화TNF-α함량강저(P＜0.05),UTI조심기병이학손상교I/R조감경.결론 오사타정감경대서심기결혈재관주손상적궤제여억제심기재관주조기TLR4적표체,감경심기염성반응유관.
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 min occlusion of left anterior descending coronary artery followed by reperfusion.Ulinastatin 1 × 104 IU/kg was injected intravenously at 5 min before reperfusion in group U,while the equal volume 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 examination and determination of myocardial apoptosis (using TUNEL),TLR4 expression (by immuno-histochemistry) 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 I/R and U (P ＜0.05).Compared with I/R group,the apoptotic index,TLR4 expression and TNF-α content were significantly decreased (P ＜ 0.05),and the pathological changes were significantly reduced in group U.Conclusion The mechanism 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.