Huang Xian-mei, Zhu Wei-hua, Kang Man-li
Children' s Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.
J Zhejiang Univ Sci. 2003 Jan-Feb;4(1):114-20. doi: 10.1631/jzus.2003.0114.
To investigate the effect of doxorubicin(DOX) on gene expression of the myocardial sarcoplasmic reticulum (SR) Ca2+ transport proteins and the mechanism of taurine (Tau) protecting cardiac muscle cells, 9 rabbits were injected with DOX, 8 rabbits with DOX and Tau, and 9 rabbits with normal saline. Cardiac function, concentration of calcium in cardiomyocytes (Myo[Ca2+]i), activity of SR Ca(2+)-ATPase (SERCA2a), level of SERCA2a mRNA and Ca2+ released channels (RYR2) mRNA were detected. The left ventricle tissues were observed by electron microscopy. The results showed that cardiac index, left ventricular systolic pressure, activity of SR Ca(2+)-ATPase and level of SERCA2a mRNA decreased, while Myo[Ca2+]i increased in DOX-treated rabbits. DOX could not affect the level of RYR2 mRNA. Tau intervention could alleviate the increase of left ventricular diastolic pressure, Myo[Ca2+]i and the decrease of SERCA2a mRNA induced by doxorubicin. The results suggested that downregulation of SERCA2a gene expression was an important mechanism of DOX-induced cardiomyopathy and that Tau could partially improve the heart function by reducing calcium overload and alleviating downregulation of SERCA2a mRNA.
为研究阿霉素（DOX）对心肌肌浆网（SR）Ca2+转运蛋白基因表达的影响及牛磺酸（Tau）保护心肌细胞的机制，将9只家兔注射DOX，8只家兔注射DOX和Tau，9只家兔注射生理盐水。检测心功能、心肌细胞内钙离子浓度（Myo[Ca2+]i）、SR Ca(2+)-ATP酶（SERCA2a）活性、SERCA2a mRNA水平及Ca2+释放通道（RYR2）mRNA水平。对左心室组织进行电镜观察。结果显示，DOX处理的家兔心脏指数、左心室收缩压、SR Ca(2+)-ATP酶活性及SERCA2a mRNA水平降低，而Myo[Ca2+]i升高。DOX不影响RYR2 mRNA水平。Tau干预可减轻DOX诱导的左心室舒张压升高、Myo[Ca2+]i升高及SERCA2a mRNA降低。结果提示，SERCA2a基因表达下调是DOX诱导心肌病的重要机制，Tau可通过减轻钙超载及缓解SERCA2a mRNA下调部分改善心功能。
