氯沙坦联合螺内酯对大鼠冠脉微栓塞后心室重构及心室功能的影响  

Effect of Spironolactone and Losartan on Ventricular Remodeling and Ventricular Function in Rats Post-Gornary Microembolization

作　　者：陈宇宁[1] 陈良龙[1] 

机构地区：[1]福建中医药大学附属第二人民医院

出　　处：《中西医结合心脑血管病杂志》2013年第7期837-839,共3页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

摘　　要：目的利用大鼠自体血栓微粒造成心肌内小冠脉栓塞,建立大鼠冠脉微栓塞(CME)模型,观察氯沙坦对CME后心室重塑及心功能的影响。方法以清洁级SD大鼠为研究对象,自心尖部注入大鼠自体血栓微粒造成心肌内微小血管栓塞,建立冠脉微栓塞模型。30只大鼠随机分成3组,即冠脉微栓塞组(ME组)和氯沙坦干预组(LO组)、螺内酯联合氯沙坦组(SL组),每组10只。术后28d取及心脏标本。HE染色观察心肌内微小梗死灶数量(Nmmi),放射免疫检测血浆血管紧张素Ⅱ(AngⅡ)血浆及心肌醛固酮(ALD)水平,Marsson染色检测心肌细胞间质胶原容积率(CVF),免疫组化法检测心肌组织TNF-α、IL-1β、活化NF-κB水平,硝酸还原比色法测定心肌组织中NO含量。超声心动图观察左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD),左室后壁厚度(LVPWT),左室短轴缩短率(LVFS)和左室射血分数(LVEF)。小动物多功能生理记录仪记录左心室舒张末期压(LVEDP),左心室收缩压(LVSP)和左心室腔内压力变化率最大值(±LVdp/dtmax)。结果 SL组均较LO组明显减少心肌各种细胞因子表达,升高组织内NO浓度,LVEDD、LVESD明显减小,LVFS明显上升,LVEF明显改善;LVEDP明显下降,±LVdp/dtmax显著上升(P<0.01)。结论螺内酯联合氯沙坦较单用氯沙坦能进一步抑制神经内分泌细胞因子激活,减轻炎症反应及氧化应激反应,减少心室重构并改善心功能。Objective To observe the effect of spironolactone plus losartan on ventricular remodeling. Methods The rat model with coronary microembolization （CME） was established by injecting a suspension of microthrombotic particles into left ventricle when clamping the ascending aorta. The microthrombotie particles were generated from the rat clots. Thirty rats were randomly divid- ed into 3 groups：CME model group （ME,n=10）,losartan group （LO,n=10）,and spironolaetone plus losartan group （SL,n=10）. The animals were sacrificed at 4 weeks after CME. A microscopy incorporated with an image analysis software （Image Pro - 6） was employed to calculate the number of micro- myocardial infarction （Nmmi） in sections with HE- staining, and measure the collagen volume fraction （CFV） in sections with Marsson - staining. Radioimmunoassay was conducted to assess the levels of angiotensin Ⅱ （Ang H ） and aldosterone （ALD）. The expressions of TNF-α, IL- 1, and activated NFκB （IOD） in myocardial tissue were detected by immunohistochemistry. Concentration of NO was analysed by speetrophotometer. And serial eehoeardiography was performed to monitor the left ventricular end - systolic and end - diastolic diameter （LVESD, LVEED） ,left ventricular short - axis fraction shorten- ing （LVFS） and ejection fraction （LVEF）. Left ventricular systolic pressure （LVSP） and end -diastolic pressure pressure （LVEDP）, and left ventricular maximum positive and negative dp/dt （ ~ LVdp/dtmax） were documented. Results Compared with losartan group,the expressions of TNF -α, IL - 1,and activated NF^B（IOD） in myocardial tissue were decreased and the level of NO was in- creased in spironolactone plus losartan group. LVEDD and LVESD were smaller with higher LVEF in spironolactone plus losartan group （P〈0.01）. LVSP and ＋ LVdp/ dtmax were increased and LVEDP was decreased in spironolactone plus losartan group （P〈0.05）. Conclusion Spironolactone plus losartan intervention could further

关 键 词：心室重构 微栓塞 神经内分泌 细胞因子 心室功能 螺内酯 氯沙坦 

分 类 号：R543[医药卫生—心血管疾病]