螺内酯对大鼠冠状动脉微栓塞后心室重构及心室功能的影响

Effect of spironolactone on ventricular remodeling and function in rats following coronary microembolization

目的采用大鼠自体血栓微粒造成心肌内小冠状动脉微栓塞(CME),观察螺内酯对CME后心室重构及心功能的影响。方法清洁级SD大鼠40只,自心尖部注入大鼠自体血栓微粒造成心肌内CME,建立CME模型。随机分对照组、假手术组、CME组和螺内酯干预组(干预组),每组10只。术后28dHE染色观察心肌内微小梗死灶数量;Marsson染色检测心肌细胞间质胶原容积率(CVF);放射免疫法检测血浆血管紧张素Ⅱ(AngⅡ)及心肌醛固酮水平;免疫组织化学法检测心肌组织TNF-α、白细胞介素(IL)-1β、NF-κB水平;硝酸还原比色法检测心肌组织NO含量。结果与假手术组比较,CME组微小梗死灶、CVF、AngⅡ、醛固酮、TNF-α、IL-1β、NF-κB明显升高(P<0.01),NO明显降低(P<0.01)。与CME组比较,干预组CVF、TNF-α、IL-1β、NF-κB、左心室舒张末和收缩末内径、左心室舒张末压明显降低,NO、左心室缩短率、LVEF等明显升高(P<0.01)。结论螺内酯能抑制相关神经内分泌-细胞因子激活,减轻炎性反应和氧化应激反应,从而减轻心室重构及改善心功能。

Objective To study the effect of spironolactone on ventricular remodeling and function in rats following coronary microembolization （CME）. Methods Forty SD rats were included in this study. A rat CME model was established by injecting microthrombotic particles into the left ventricle. The rats were randomly divided into control group, sham-operation group, CME group and spironolactone treatment group （10 in each group）. The number of microinfarction foei in myocardium was observed with HE staining,the serum levels of AngII and aldosterone （ALD） were measured by radioimmunoassay,the collagen volume fraction （CVF） in myocardiocytes was measured with Marsson staining, the expressions of TNF-α,IL 1β and activated NF-κB in myocardial tissue were detected by immunohistochemistry,and the serum NO level in myocardial tissue was measured by spectrophotometry 28 days after operation. Results The number of microinfarction foci, CVF, serum levels of Ang II and ALD, expression levels of TNF-α, IL-1β and activated NF-κB were significantly higher whereas the serum NO level was significantly lower in CME group than in sham-operation group （P〈0.01）. The CVF, expression levels of TNF-α, IL-β and activated NF-κB,inner diameter of left ventricle at end-diastolic and stolic phase,and left ventricular pressure at end-diastolic phase were significantly lower whereas the serum No level and LVEF were significantly higher in spironolactone treatment group than in CME group （P〈0.01）. Conclusion Spironolactone can inhibit the activation of neuroendocrine cytokines and reduce the inflammatory and oxidative stress reactions,thus improving the ventricular remodeling and function.