Li Shufeng, E Mingyan, Yu Bo
Department of Cardiology, Second Affiliated Hospital of Harbin medical University, 246 Xuefu Road, Harbin, 150086, PR China.
Mol Biol Rep. 2008 Dec;35(4):489-94. doi: 10.1007/s11033-007-9112-4. Epub 2007 Jun 19.
Adriamycin is one of the most effective and useful antineoplastic agents. Acute doxorubicin cardiotoxicity involved cardiomyocyte apoptosis. In this study, we investigated whether adriamycin induced myocardium apoptosis through activation of nuclear factor kappaB in rat. Forty male Wistar rats were randomly divided into five groups: control, ADR 5 mg/kg, ADR 10 mg/kg, ADR 15 mg/kg group and ADR + PDTC 200 mg/ml group. Myocardial apoptosis was detected by DNA fragmentation assay and TUNEL assay; Location and distribution of p-IkappaB alpha was observed by immunohistochemical assay; Myocardial expression of p-IkappaB alpha protein was assessed by Western blot analysis; Activity of NF-kappaB was evaluated by Electrophoretic Mobility Shift Assay. The myocardial apoptotic index, expression of p-IkappaB alpha, and binding activity of NF-kappaB increased significantly in ADR groups in dose-dependent manner. PDTC as a nonspecific inhibitor of NF-kappaB protected myocardium from apoptosis by inhibiting NF-kappaB activation. Adriamycin induces myocardium apoptosis through activation of nuclear factor kappaB in rat and NF-kappaB activation requires IkappaB alpha degradation.
阿霉素是最有效且实用的抗肿瘤药物之一。急性阿霉素心脏毒性涉及心肌细胞凋亡。在本研究中，我们调查了阿霉素是否通过激活大鼠核因子κB诱导心肌凋亡。40只雄性Wistar大鼠随机分为五组：对照组、阿霉素5mg/kg组、阿霉素10mg/kg组、阿霉素15mg/kg组和阿霉素+200mg/ml吡咯烷二硫代氨基甲酸盐（PDTC）组。采用DNA片段化分析和TUNEL分析检测心肌凋亡；通过免疫组织化学分析观察磷酸化κBα（p-IκBα）的定位和分布；采用蛋白质印迹分析评估心肌p-IκBα蛋白的表达；通过电泳迁移率变动分析评估核因子κB（NF-κB）的活性。阿霉素各剂量组心肌凋亡指数、p-IκBα表达及NF-κB结合活性均呈剂量依赖性显著增加。PDTC作为NF-κB的非特异性抑制剂，通过抑制NF-κB激活保护心肌免于凋亡。阿霉素通过激活大鼠核因子κB诱导心肌凋亡，且NF-κB激活需要κBα降解。
