Department of Cardiology, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai 200080, PR China.
Mol Med Rep. 2012 Feb;5(2):400-4. doi: 10.3892/mmr.2011.636. Epub 2011 Oct 18.
Nuclear factor κB (NF-κB) is activated by a wide range of inducers and is able to mediate gene transcription. We investigated the role of NF-κB in adriamycin-induced myocardial injury in rats and its mechanism of action. A total of 30 male Wistar rats were randomly divided into 3 groups: control, anthracycline antibiotic adriamycin (ADR) and ADR + pyrrolidine dithiocarbamate (PDTC). Myocardial apoptosis was detected by TUNEL assay; myocardium p53 gene expression was examined by RT-PCR analysis; location and distribution of p53 was observed by immunohistochemical assay; myocardial expression of p53 protein was assessed by Western blot analysis and activity of NF-κB was evaluated by electrophoretic mobility shift assay. The binding activity of NF-κB, myocardial apoptotic index and expression of p53 increased significantly in the ADR groups. All of these changes induced by ADR were inhibited by PDTC. It was concluded that NF-κB activation may be pro-apoptotic through regulation of the expression of p53 in adriamycin-induced myocardial injury.
核因子 κB（NF-κB）可被广泛的诱导物激活，并能介导基因转录。我们研究了 NF-κB 在阿霉素诱导的大鼠心肌损伤中的作用及其作用机制。30 只雄性 Wistar 大鼠随机分为 3 组：对照组、蒽环类抗生素阿霉素（ADR）组和 ADR+吡咯烷二硫代氨基甲酸盐（PDTC）组。通过 TUNEL 检测法检测心肌细胞凋亡；通过 RT-PCR 分析检测心肌 p53 基因表达；通过免疫组织化学法观察 p53 的定位和分布；通过 Western blot 分析评估 p53 蛋白的心肌表达；通过电泳迁移率变动分析评估 NF-κB 的活性。ADR 组 NF-κB 的结合活性、心肌细胞凋亡指数和 p53 表达均显著增加。ADR 引起的所有这些变化均被 PDTC 抑制。结论：NF-κB 的激活可能通过调节 p53 的表达而导致阿霉素诱导的心肌损伤发生促凋亡作用。
