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。%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 .
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