CAJ | 학술논문

目的探讨红细胞生成素(EPO)对阿霉素(DOX)性心肌病的预防性保护作用及可能机制.方法 31只Wistar大鼠随机分为DOX组(12只)、DOX+EPO组(11只)和对照组(8只),前2组采用腹腔注射DOX建立扩张型心肌病模型,并在腹腔注射DOX前分别予生理盐水或EPO预防性干预.测量3组大鼠血流动力学以了解左室收缩功能变化;Masson氏染色法观察心脏组织病理学变化;TUNEL法分析心肌细胞的凋亡;Western印迹法检测Bax和Bcl-2的蛋白表达.结果 DOX组和DOX+EPO组左室收缩功能差异有统计学意义(P<0.05),DOX+EPO组的心肌纤维化面积比率(7.49±1.11)%明显比DOX组(12.14±1.07)%降低(P<0.05).DOX组和DOX+EPO组凋亡指数分别为(0.93±0.08)%和(0.16+0.04)%(P<0.05).Western印迹显示,DOX组中Bcl-2蛋白表达水平低于对照组,DOX+EPO组Bcl-2的表达水平明显高于DOX组,差异均有统计学意义(P<0.05).结论 EPO可能通过上调Bcl-2蛋白表达发挥抗凋亡作用,从而对阿霉素性心肌病发挥预防性保护作用.
목적 탐토홍세포생성소(EPO)대아매소(DOX)성심기병적예방성보호작용급가능궤제.방법 31지Wistar대서수궤분위DOX조(12지)、DOX+EPO조(11지)화대조조(8지),전2조채용복강주사DOX건립확장형심기병모형,병재복강주사DOX전분별여생리염수혹EPO예방성간예.측량3조대서혈류동역학이료해좌실수축공능변화;Masson씨염색법관찰심장조직병이학변화;TUNEL법분석심기세포적조망;Western인적법검측Bax화Bcl-2적단백표체.결과 DOX조화DOX+EPO조좌실수축공능차이유통계학의의(P<0.05),DOX+EPO조적심기섬유화면적비솔(7.49±1.11)%명현비DOX조(12.14±1.07)%강저(P<0.05).DOX조화DOX+EPO조조망지수분별위(0.93±0.08)%화(0.16+0.04)%(P<0.05).Western인적현시,DOX조중Bcl-2단백표체수평저우대조조,DOX+EPO조Bcl-2적표체수평명현고우DOX조,차이균유통계학의의(P<0.05).결론 EPO가능통과상조Bcl-2단백표체발휘항조망작용,종이대아매소성심기병발휘예방성보호작용.
Objective To investigate the preventive effect and potential mechanisms of erythropoietin (EPO) against doxorubicin (DOX)-induced cardiomyopathy. Methods Thirty-one Wistar rats were randomly divided into DOX group (n=12) , DOX + EPO group (n=11) and control group (n=8). Dilated cardiomyopathy was induced by intraperitoneal injection of DOX for both DOX group and DOX+EPO group, and normal saline or EPO was administered before DOX injection for preventive purpose. Left ventricular systolic function was evaluated by invasive haemodynamic measurements among three groups. Rats were then sacrificed for Masson-stained histopathology observation and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) analysis of apoptosis, with immunological detection for Bax and Bcl-2 by Western blotting. Results There was significant difference in left ventricular systolic function between DOX group and DOX+EPO group. The area ratio of myocardial fibrosis was significantly decreased from (12.14±1.07)% in the DOX group to (7.49±1.11)% in the DOX+EPO group (P<0.05). The apoptotic index was (0.93±0.08)% and (0.16±0.04)% in the DOX group and DOX + EPO group (P<0.05) , respectively. Western blotting showed that Bcl-2 protein expression was decreased in DOX group compared to control group, but significantly increased in the DOX + EPO group compared to DOX group (P<0.05). Conclusions EPO can protect against DOX-induced cardiomyopathy via anti-apoptotic pathways. The up-regulation of Bcl-2 protein expression may contribute to the protection.