晚期糖基化终产物改变心肌细胞自发钙火花形态学  

Advanced glycation end products change spontaneous calcium spark morphology in cardiomyocytes

作　　者：邓建新[1,2] 刘文娟[3] 林泽勋 王永辉[3] 阎德文[1] 

机构地区：[1]深圳大学第一附属医院内分泌科,广东深圳518060 [2]南方医科大学病理生理学教研室,广东广州510515 [3]深圳大学医学院病理生理学教研室,广东深圳518060

出　　处：《中国病理生理杂志》2014年第11期2076-2078,2083,共4页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81200122)

摘　　要：目的:本研究旨在探讨晚期糖基化终末产物(AGEs)对心肌细胞雷诺丁受体(RyR)活性的影响及钙调控作用,从而阐明糖尿病心肌病心脏功能障碍的潜在机制。方法:通过激光共聚焦显微成像技术在培养的乳鼠心肌细胞观察自发钙火花发放频率以及钙火花的形态。结果:与对照组相比,AGEs大幅度增加钙火花的发放频率,其中10 mg/L AGEs组增加48%(P<0.01),50 mg/L组AGEs增加200%(P<0.01);而150 mg/L组AGEs组增加110%(P<0.01)。AGEs改变自发钙火花的形态、降低钙火花的幅度、宽度和钙火花持续时间并增加心肌细胞静息期钙离子水平。结论:AGEs引起自发钙火花的发放频率,从而增强钙火花介导的肌浆网Ca2+漏流,增加心肌细胞静息期钙离子水平,这可能是引起糖尿病性心肌病收缩功能障碍的重要原因。AIM： To investigate the effect of advanced glycation end products（ AGEs） on the activity of rynodine receptor（ RyR） and calcium regulation in cardiomyocytes,in order to clarify the underlying mechanisms of cardiac dysfunction in diabetic cardiomyopathy. METHODS： The frequency and morphology of spontaneous calcium sparks were observed in cultured neonatal rat ventricular myocytes by the imaging technique of laser scanning confocal microscope. RESULTS： Compared with control group,AGEs increased the frequency of calcium sparks,where 10 mg / L of AGEs increased by 48%（ P〈0. 01）,50 mg / L of AGEs increased by 200%（ P〈0. 01） and 150 mg / L of AGEs increased by110%（ P〈0. 01）. AGEs alter the morphology of spontaneous calcium sparks. AGEs decreased the amplitude and width of calcium sparks,and calcium spark duration. AGEs increased the level of cardiomyocyte resting Ca2 ＋. CONCLUSION：AGEs increases the frequency of spontaneous calcium sparks,thereby enhancing calcium spark-mediated leaking of sarcoplasmic reticulum Ca2 ＋,which may be the cause of diabetic cardiomyopathy systolic dysfunction.

关 键 词：晚期糖基化终产物 心肌细胞 钙火花 兴奋-收缩偶联 

分 类 号：R363[医药卫生—病理学]