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目的研究NF-κB在大鼠阿霉素心肌病中的变化及意义。方法60只雄性Wistar大鼠,随机分为3组:对照组、ADR组、ADR+PDTC组。实验第30天,光镜下观察心肌组织病理形态学改变;免疫组化法检测NF-κBp50在心肌组织中的位置及分布;免疫印迹法检测心肌组织细胞核中NF-κBp50蛋白的表达;凝胶阻滞分析法检测NF-κB结合活性变化;RT-PCR法测定心肌组织中p53mRNA的表达。结果光镜下心肌组织病理损害程度,ADR+PDTC组较ADR组轻。与对照组比较,ADR组心肌组织中见大量阳性表达NF-κBp50的心肌细胞核;胞核呈阳性表达NF-κBp50的部位位于心外膜下,与心肌组织病理改变部位基本一致;ADR组心肌细胞核中NF-κBp50蛋白表达显著增加(P<0.05);ADR组心肌组织中NF-κB结合活性显著增加(P<0.05)。ADR组心肌组织中p53mRNA表达显著增加(P<0.05)。结论在大鼠阿霉素心肌病中NF-κB的活性增加,NF-κB与阿霉素致大鼠心肌病理损伤和凋亡相关基因p53的表达有关。
Objective To study the changes and significance of NF-κB in doxorubicin cardiomyopathy in rats. Methods Sixty male Wistar rats were randomly divided into three groups: control group, ADR group and ADR + PDTC group. On the 30th day, the histopathological changes of myocardium were observed under light microscope. The location and distribution of NF-κBp50 in myocardium were detected by immunohistochemistry. The expression of NF-κBp50 protein in the nucleus of myocardium was detected by Western blotting. The changes of NF-κB binding activity were detected by blocking assay. The expression of p53 mRNA in myocardium was detected by RT-PCR. Results Under light microscope, the degree of pathological damage in myocardium was lighter than that in ADR group. Compared with the control group, a large number of myocardial nuclei of NF-κBp50 positive cells were found in the myocardium of ADR group. NF-κBp50 positive cells in the nucleus were located in the epicardium and were consistent with the pathological changes in the myocardium. NF-κBp50 protein expression was significantly increased (P <0.05); NF-κB binding activity was significantly increased in ADR group (P <0.05). The expression of p53 mRNA in myocardium of ADR group was significantly increased (P <0.05). Conclusions The activity of NF-κB in adriamycin-induced cardiomyopathy is increased in rats. NF-κB is associated with myocardial injury induced by doxorubicin and the expression of p53.