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坎地沙坦对兔心肌缺血再灌注微血管功能障碍的影响

Protection of candesartan on myocardial microvascular dysfunction in rabbit model of ischemia-reperfusion
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摘要 目的探讨坎地沙坦预处理对兔心肌缺血/再灌注(I/R)微血管功能障碍的影响。方法 40只健康雄性新西兰大白兔随机分为假手术组、心肌I/R模型组、坎地沙坦低剂量组(0.5 mg/kg)、中剂量组(2.5mg/kg)、高剂量组(5.0 mg/kg),每组8只。造模前各组灌胃给药2周。假手术组左前降支近端穿线但不结扎,其余4组予60 min缺血,360 min再灌注。取缺血梗死区心肌组织,HE染色后计算微血管腔内中性粒细胞数及心肌灶性出血发生率;采用硝酸还原酶法检测心肌组织一氧化氮(NO)水平,免疫组化法测定内皮型一氧化氮合酶(eNOS)表达;透射电镜观察毛细血管超微结构。结果与模型组比较,坎地沙坦低剂量组、中剂量组、高剂量组微血管腔内中性粒细胞数、心肌灶性出血发生率均明显减少(P<0.01),心肌组织NO含量、eNOS表达均明显增加(P<0.01),并呈剂量依赖性;电镜示坎地沙坦低剂量组、中剂量组、高剂量组毛细血管内皮细胞肿胀均较模型组减轻。结论坎地沙坦可上调eNOS的表达,升高NO水平,缓解血管内皮细胞肿胀,保护微血管的完整性,抑制中性粒细胞黏附聚集,缓解微血管堵塞,从而改善兔心肌I/R微血管功能障碍,且该作用具有一定的剂量依赖性。 Objective To investigate the effect of pretreatment with candesartan on myocardial microvascular dysfunction in rabbit model of ischemia-reperfusion(I/R).Methods Healthy male New Zealand white rabbits were randomly divided into five groups(n =8 each): sham-operation group,myocardial I/R model group,candesartan low-dose group(0.5 mg/kg per day),candesartan middle-dose group(2.5 mg/kg per day),candesartan high-dose group(5 mg/kg per day).After intragastric administration for 2 weeks,the left anterior descending(LAD) coronary artery was occluded for 60 m followed by 360 m reperfusion to induce ischemia-reperfusion injury.After stained with hematoxylin and eosin(HE),the percentage of myocardium focal bleeding incidence and the quantity of neutrophils in capillary lumen were determined by light microscopy.Nitrogen monoxidum(NO) in myocardium was evaluated by nitrate reductase method.The expression of endothelial nitricoxide synthase(eNOS) was analyzed by immunohistochemical technique.The ultramicrostructure of capillary was observed by transmission electron microscope.Results Compared with model group,the quantity of neutrophils in capillary lumen and the percentage of myocardium focal bleeding incidence were significantly reduced while the level of NO and the expression of eNOS were significantly increased by candesartan in a dose-dependent manner(P 0.01).It was shown in the transmission electron microscope that the swelling of vascular endothelial cells was limited in candesartan low-dose group,middle-dose group and high-dose group.Conclusions Candesartan could protect microvascular dysfunction by up-regulating the expression of eNOS,increasing the level of NO,depressing the aggregation and adherence of neutrophils,limiting the swelling of vascular endothelial cells and protecting the integrity of capillary in a dose-dependent manner in this rabbit I/R model.
出处 《中国现代医学杂志》 CAS CSCD 北大核心 2011年第13期1458-1462,共5页 China Journal of Modern Medicine
基金 广西科学基金(No:桂科基0575069)
关键词 心肌缺血/再灌注 微血管功能障碍 坎地沙坦 myocardial ischemia-reperfusion microvascular dysfunction candesartan
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