CAJ | 학술논문

目的：观察肾素-血管紧张素阻断剂缬沙坦预处理后大鼠心肌缺血再灌注损伤中血管紧张素受体AT2R的表达与冠状动脉重构。方法：将123只大鼠随机分成3组：假手术（Sham）组、对照（Control）组、缬沙坦（ARB）组。术前假手术组、对照组给予生理盐水灌胃，缬沙坦组给予缬沙坦10 mg · kg -1· d-1灌胃4周，对照组、缬沙坦组予以手术开胸结扎大鼠心脏左冠状动脉前降支30 min后松脱结扎线建立缺血再灌注（I-R）损伤动物模型，假手术组开胸不结扎，术后各组继续用生理盐水、缬沙坦灌胃，分别于术后3、7、14、28 d 4个时间点测量左心室舒缩压后处死大鼠并采集大鼠心脏标本。予天狼猩红染色、免疫组化链霉素亲和素-生物素-过氧化酶复合物（SABC）观察冠状动脉重构、冠周胶原沉积以及AT2R在冠状动脉的定位、表达的动态变化。结果免疫组化分析显示AT2R定位于冠状动脉外膜呈放射状分布，尤以大血管管周密度较高，冠状动脉内膜也有部分表达。AT2R呈一过性表达，对照组I-R术后7 d时达峰值，缬沙坦组较对照组AT2R表达峰值提高、提前。I-R术后3 d心脏舒张功能受损；缬沙坦组左心室舒张末压（LVEDP）显著性低于对照组。缬沙坦组冠周间质胶原沉积于术后28 d显著性低于对照组；对照组心肌冠状动脉周围胶原沉积随时间进展逐渐升高，术后14、28 d显著高于Sham组。结论：缬沙坦可能通过心肌I-R损伤后AT2R的一过性高表达来抑制冠状动脉重构而保护心功能。
목적：관찰신소-혈관긴장소조단제힐사탄예처리후대서심기결혈재관주손상중혈관긴장소수체AT2R적표체여관상동맥중구。방법：장123지대서수궤분성3조：가수술（Sham）조、대조（Control）조、힐사탄（ARB）조。술전가수술조、대조조급여생리염수관위，힐사탄조급여힐사탄10 mg · kg -1· d-1관위4주，대조조、힐사탄조여이수술개흉결찰대서심장좌관상동맥전강지30 min후송탈결찰선건립결혈재관주（I-R）손상동물모형，가수술조개흉불결찰，술후각조계속용생리염수、힐사탄관위，분별우술후3、7、14、28 d 4개시간점측량좌심실서축압후처사대서병채집대서심장표본。여천랑성홍염색、면역조화련매소친화소-생물소-과양화매복합물（SABC）관찰관상동맥중구、관주효원침적이급AT2R재관상동맥적정위、표체적동태변화。결과면역조화분석현시AT2R정위우관상동맥외막정방사상분포，우이대혈관관주밀도교고，관상동맥내막야유부분표체。AT2R정일과성표체，대조조I-R술후7 d시체봉치，힐사탄조교대조조AT2R표체봉치제고、제전。I-R술후3 d심장서장공능수손；힐사탄조좌심실서장말압（LVEDP）현저성저우대조조。힐사탄조관주간질효원침적우술후28 d현저성저우대조조；대조조심기관상동맥주위효원침적수시간진전축점승고，술후14、28 d현저고우Sham조。결론：힐사탄가능통과심기I-R손상후AT2R적일과성고표체래억제관상동맥중구이보호심공능。
Objective To observe the expression of angiotensin Ⅱ type 2 receptor (AT2R) and coronary arterial remodeling in ischemia-reperfusion(I-R) injury rat after the renin -angiotensin blocker valsartan pretreatment .Methods 123 rats were random-ly divided into 3 groups :sham -operation group(sham) ,control group and valsartan group(ARB) .The control group and the sham group received the gavage of normal saline and the ARB group received valsartan gavage 10 mg/(kg · d) for 4 weeks before surger-y .The I-R injury rat model was established by thoracotomy for ligating the left anterior descending (LAD) coronary artery and re-moving the ligation after 30 min .The sham group was performed the thoracotomy without ligation .At the 4 timepoints of postoper-ative 3 ,7 ,14 ,28 d ,the left ventricular diastolic and systolic pressures were measured ,then the rats were killed for collecting the rat heart sample .The section was stained by sirius red .The collagen deposition in coronary arterial remodeling and coronary arterial pe-ripheral area ,and the dynamic change of location and expression of AT2R in the coronary artery were observed by the immunohisto-chemical streptavidinbiotin peroxidase complex (SABC) .Results The immunohistochemical analysis revealed that AT 2R was local-ized in the adventitia of coronary arteries with the radial distribution ,showing the higher density especially in large coronary arterial peripheral area ,the partial expression existed in the coronary arterai intima .The expression of AT2R was transient ,which on 7 d af-ter I-R operation in the control group reached the peak value ,while the expression peak value of AT2R in the valsartan group was higher and earlier than that in the control group .The heart diastolic function on 3 d after I-R operation was impaired ;the left ven-tricular end diastolic presure (LVEDP) in the valsartan group was significantly lower than that in the control group .The collagen deposition of coronary peripheral mesenchyma on postoperative 28 d in the valsartan group was significantly lower than that in the control group;the coronary peripheral collagen deposition in the control group was gradually increased with the time progression , which on postoperative 14 ,28 d was significantly higher than that in the sham group .Conclusion Valsartan could inhibit the coronary arterial remodeling for protecting the heart function possible by the transient high AT 2R expression after myocardial I-R injury .