Burke Briant E, Olson Richard D, Cusack Barry J, Gambliel Herve A, Dillmann Wolfgang H
Center for Biomedical Research, Boise, ID 83706, USA.
Biochem Biophys Res Commun. 2003 Apr 4;303(2):504-7. doi: 10.1016/s0006-291x(03)00275-4.
Chronic anthracycline administration results in a time- and dose-dependent cardiomyopathy. The Ca-ATPase of the sarcoplasmic reticulum, SERCA2, has been implicated as a principal target for anthracycline-induced cardiotoxicity. This hypothesis predicts that improved SERCA2 function would provide protection from cardiotoxic effects of anthracycline administration. Doxorubicin was administered (1.7 mg/kg three times weekly; cumulative dose of 20 mg/kg) to 10 transgenic mice that overexpressed SERCA2 and to 10 isogenic littermates. Survival was monitored for 60 days and histologic comparisons were made of cardiac tissue. Survival in the transgenic mice was worse (1/10 60-day survivors) compared to isogenic control mice (7/10 60-day survivors). There was a greater degree of histologic damage exhibited in hearts from transgenic mice compared to isogenic controls when all available hearts were examined. These data do not support a role of SERCA2 in ameliorating anthracycline cardiotoxicity.
长期给予蒽环类药物会导致时间和剂量依赖性的心肌病。肌浆网的钙 - 腺苷三磷酸酶（SERCA2）被认为是蒽环类药物诱导心脏毒性的主要靶点。该假说预测，改善SERCA2功能将为蒽环类药物给药的心脏毒性作用提供保护。对10只过表达SERCA2的转基因小鼠和10只同基因的同窝小鼠给予阿霉素（1.7mg/kg，每周三次；累积剂量20mg/kg）。监测60天的存活率，并对心脏组织进行组织学比较。与同基因对照小鼠（7/10为60天存活者）相比，转基因小鼠的存活率更低（1/10为60天存活者）。当检查所有可用心脏时，与同基因对照相比，转基因小鼠心脏的组织学损伤程度更大。这些数据不支持SERCA2在减轻蒽环类药物心脏毒性方面的作用。
