叶酸对阿霉素所致心肌损伤的保护作用研究  

Folic acid protects against doxorubicin-induced cardiotoxicity

作　　者：叶盛[1] 夏武杰 张新民[1] 陈鹏[1] 

机构地区：[1]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,325027

出　　处：《浙江医学》2017年第22期1995-1997,2015,共4页Zhejiang Medical Journal

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Western blot法分析凋亡相关蛋白Ba x、Bc l-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。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.

关 键 词：阿霉素 叶酸 心脏毒性 

分 类 号：R730.53[医药卫生—肿瘤]