摘要
目的观察阿霉素所致心衰大鼠心肌ErbB4蛋白表达和细胞凋亡及NRG-1β的干预作用。方法用60只SD雄性大鼠随机分为4组:阿霉素心肌病8周组(ADR1,n=10),阿霉素2 mg/kg,尾静脉注射,每周1次,连续注射8周;阿霉素心肌病12周组(ADR2,n=20),阿霉素2 mg/kg,尾静脉注射,每周1次,连续注射8周,之后普通喂养到12周;阿霉素心肌病+NRG-1治疗组(NRG,n=20),在注射ADR后8周后即开始给予neuregulin-1β10μg/(kg.d)尾静脉注射,连续5 d,之后喂养到12周;正常对照组(CON,n=10)。免疫印迹法(Western blot)检测ErbB4受体蛋白的表达;HE染色病理观察评分;TUNEL法观察心肌细胞凋亡。结果心肌细胞凋亡指数:与模型组相比,NRG治疗组凋亡指数显著降低(P<0.05);ErbB4蛋白表达:模型组第8周时表达明显高于正常组,模型组12周时表达较正常组明显减少;与模型组比较,NRG干预组ErbB4蛋白表达明显上调(P<0.05)。结论ErbB4蛋白表达在扩张型心肌病大鼠心肌中表达早期增强,随着病程延长明显下降;NRG-1β能够抑制扩张型心肌病大鼠心肌细胞凋亡并增加其受体ErbB4的表达。
Objective To study the adriamycin （ADR）-induced expression of ErbB4 in and apoptosis of cardiac muscle cells of rats with dilated cardiomyopathy and their intervention with neuregnlin-1β. Methods Sixty male SD rats, weighing 200 - 250 g, were randomly divided into ADR 1 group （ n = 10 ）, ADR 2 group （ n = 20） , ADR ＋ neuregulin-1β group （ n = 20 ） , and normal control （ NC ） group （ n = 10）. Rats in ADR1 and ADR2 groups were injected with 2.0 mg/kg of ADR through the tail vein, once a week for 8 and 12 weeks, respectively. Rats in ADR ＋ neuregulin-1β group were injected with 2.0mg/kg of ADR through the tail vein, once a week for 8 weeks, followed by neuregulin-1β [ 10 μg/（ kg · d） ] , once a day for 5 d. Rats in NC group received normal saline [ 2 ml/（ kg · d） ], once a week for 8 weeks. Expression of ErbB4 was detected by Western blotting. Lesions of cardiac muscle were scored with HE staining. Apoptosis of cardiac muscle cells was de tected with the TUNEL method. Results The apoptotic index of cardiac muscle ceils was significantly lower in ADR ＋neuregnlin-1β group than in ADR 1 group （P 〈0.05）. The expression level of ErbB4 was significantly higher in ADR 1 group than in NC group and obviously lower in ADR 2 group than in NC group, and significantly higher in ADR ＋ neuregulin-1β group than in ADR2 group （ P 〈 0.05 ）. Conclusion Early ErbB4 expression in- creases in cardiac muscle ceils of rats with dilated cardiomyopathy and decreases with the prolonged disease course. Neuregnlin-1β can inhibit the apoptosis of and increase the ErbB expression in cardiac muscle cells.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2010年第3期261-264,共4页
Journal of Third Military Medical University
