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机构地区:[1]中山大学附属第二医院内分泌科,广东广州510120
出 处:《中山大学学报(医学科学版)》2010年第3期321-326,共6页Journal of Sun Yat-Sen University:Medical Sciences
基 金:"十五"国家科技攻关重大计划(2004BA720A29);广东省科技计划项目(2008B050100010)
摘 要:【目的】探讨单纯过量醛固酮在正盐饮食和正常血钾情况下对SD大鼠心肌结构的影响及其可能机制。【方法】正盐饮食和补钾情况下,雄性SD大鼠随机分3组:对照组、醛固酮组和醛固酮+安体舒通组,每组10只。观察4周,每周测量血压,实验结束时观察心肌结构改变,比色法测定血清和心肌丙二醛(MDA)水平和过氧化物歧化酶(SOD)活性,ELISA法测定血清超敏C反应蛋白(hsCRP)水平,免疫组化法检测心肌ED-1表达,实时荧光PCR法检测p47phox和p22phox基因表达。【结果】醛固酮作用4周,SD大鼠血压轻微上升(P<0.05),但心肌超微结构已有改变;同时,血清和心肌MDA水平和SOD活性、心肌p47phox基因表达以及血清hsCRP水平均增加(P均<0.05),但心脏局部未见炎症细胞浸润。安体舒通可逆转醛固酮的影响,且不完全依赖血压的下降。【结论】单纯过量醛固酮在正盐饮食和正常血钾情况下可引起SD大鼠心肌受损和氧化应激反应增强,这些变化先于心脏局部炎症反应的出现。【Objective】To investigate the direct cardiac injury of aldosterone alone in SD rats under normal salt diet and normokalemia and its possible mechanism.【Methods】Male SD rats receiving normal salt diet and potassium chloride supplementation for 4 weeks were divided into three groups(n=10 in each group):control;aldosterone infusion;aldosterone infusion plus spironolactone.Systolic blood pressure(SBP)was measured every week.At the end of experiment,the myocardial structure was observed,malonaldehyde(MDA)and superoxide dismutase(SOD)activity in serum and cardiac tissue were estimated by colorimetry,serum hsCRP concentration was assayed by ELISA,ED-1 expression of myocardium was analyzed by immunohistochemistry,p47phox and p22phox mRNA expression were measured using real-time RT-PCR.【Results】Aldosterone,under a normal salt diet and normokalemia,induced only a slight increase in the SBP of SD rats(P0.05).However,aldosterone significantly induced cardiac ultrastructure changes.Furthermore,aldosterone increased MDA formation and SOD activity in serum and heart tissue(P0.05),increased the level of serum hsCRP and the expression of cardiac p47phox mRNA(P0.05).Simultaneously,no significant infiltration of monocyte/macrophage can be seen in the mesenchyme of myocardium.The effect of aldosterone was reversed by spironolactone,which was partly independent of SBP.【Conclusion】Excess aldosterone alone can induce cardiac damage and severe oxidative stress response before emergence of inflammation,even in the absence of salt loading and hypokalemia.
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