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叶酸对阿霉素所致心肌损伤的保护作用研究
叶盛, 夏武杰, 张新民, 陈鹏
温州医科大学附属第二医院、温州医科大学育英儿童医院心血管内科
摘要:
目的探讨叶酸对阿霉素所致心肌损伤的保护作用。方法将24只小鼠随机分成4组:对照组,叶酸组,阿霉素组,阿霉素+叶酸组,每组6只。阿霉素组:采用腹腔内注射阿霉素(每次2.5mg/kg,每周3次,共6次,总量15mg/kg),建立小鼠阿霉素心脏毒性模型,常规喂养4周;叶酸组:以等量0.9%氯化钠溶液代替阿霉素作腹腔内注射,并给予叶酸灌胃[10mg/(kg·d),共4周];阿霉素+叶酸组:按上两组方法和剂量给予阿霉素和叶酸。对照组:以等量0.9%氯化钠溶液代替阿霉素做腹腔内注射,常规喂养4周。4周后B超测定小鼠心脏功能,TUNEL法测定小鼠心肌细胞凋亡率,并利用Westernblot法分析凋亡相关蛋白Bax、Bcl-2的表达。结果阿霉素组各项心功能指标、心肌细胞凋亡率、Bax/Bcl-2比值与对照组比较均有统计学差异(均P<0.05);而阿霉素+叶酸组各项心功能指标、心肌细胞凋亡率、Bax/Bcl-2比值与阿霉素组比较均有明显改善(均P<0.05)。结论叶酸对小鼠阿霉素心肌损伤有明显的保护作用。
关键词:  阿霉素 叶酸 心脏毒性
DOI:10.12056/j.issn.1006-2785.2017.39.22.2017-2010
分类号:
基金项目:
Folic acid protects against doxorubicin-induced cardiotoxicity
the Second Affiliated Hospital of Wenzhou Medical University
Abstract:
Objective To investigate the protective effects of folic acid(FA) in the pathogenesis of doxorubicin(DOX)- induced cardiotoxicity. Methods Twenty four mice were randomly divided into 4 groups: control group, folic acid group, doxorubicin group and doxorubicin+ folic acid group with 6 mice in each group. Mice in doxorubicin group received doxorubicin (2.5 mg/kg, i.p, 3/wk for 2 wks,); mice in folic acid group received FA 10 mg/d by gavage for 4 wks; mice in doxorubicin+folic acid group received FA10 mg/d by gavage from the day of DOX administration for 4 wks; mice in control group received injections of saline. After 4 weeks, left ventricular (LV) function was measured by echocardiography, cardiomyocyte apoptosis were assessed by TUNEL staining; the expression of bax/bcl-2 was detected by Western blot. Results Doxorubicin induced left ventricular dysfunction and remolding (P<0.05), increased cardiomyocyte apoptosis (P<0.05), and up-regulated of bax/bcl-2 levels (P< 0.05). FA ameliorated DOX-induced left ventricular dysfunction and remolding(P<0.05), attenuated cardiomyocyte apoptosis(P< 0.05), and down-regulated bax/bcl-2 expression(P<0.05). Conclusion Folic acid has a protective effect against DOX-induced cardiotoxicity in mice.
Key words:  doxorubicin ( DOX) folic acid( FA) cardiotoxicity