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中国癌症防治杂志

中国癌症防治杂志 ›› 2013, Vol. 5 ›› Issue (2): 105-109.doi: 10.3969/j.issn.1674-5671.2013.02.05

• 基础研究 • 上一篇    下一篇

曲美他嗪对阿霉素化疗的乳腺癌荷瘤裸鼠心肌能量代谢的影响

  

  1. 广西医科大学附属肿瘤医院麻醉科；广西医科大学研究生学院；广西医科大学附属肿瘤医院妇瘤科
  • 出版日期:2013-06-25 发布日期:2013-06-27
  • 通讯作者: 何并文 E-mail:bingwenhe@aliyun.com
  • 基金资助:

    广西留学回国人员基金资助项目（桂科回0991018）

Effects of trimetazidine on myocardial energy metabolism after adriamycin chemotherapy in a nude mouse breast cancer model

  • Online:2013-06-25 Published:2013-06-27

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被引次数

6

摘要： 目的 研究曲美他嗪（TMZ）对阿霉素（ADM）化疗的乳腺癌荷瘤裸鼠心肌能量代谢的影响，以探讨其对ADM化疗诱导心肌损伤的保护作用及其可能的作用机制。方法 将接种成功的乳腺癌荷瘤裸鼠27只，随机分成3组：A组（对照组）予腹腔注射生理盐水10 ml/kg；B组、C组予腹腔注射ADM 2.5 mg/kg，均为每周2次，共4周，建立乳腺癌裸鼠心肌毒性模型。从第3周开始，C组给予TMZ 20 mg/（kg·d）灌胃，A组、B组分别给予与C组等容的生理盐水灌胃，1次／日，共14 d。最后一次给药的第2天麻醉裸鼠，每组裸鼠分别于灌胃前（T1）、麻醉前（T2）、麻醉后30 min（T3）各取血液0.2 ml，并留取心肌组织标本。用酶联免疫吸附法测定各时间点的血清心肌肌钙蛋白I（cTnI）的水平和心肌线粒体长链3-酮脂酰辅酶A 硫解酶（3-KAT）的活性；用高效液相色谱法测定心肌组织中三磷酸腺苷（ATP）、二磷酸腺苷（ADP）的含量。结果 ① B组、C组T1时点的cTnI值均显著高于A组（P＜0.05），而B组、C组比较差异则无统计学意义（P＞0.05）；C组T2、T3时点的cTnI值显著低于B组（P＜0.05）。A组3个时点的cTnI值比较差异无统计学意义（P＞0.05）。B组、C组3个时点的cTnI值比较差异有统计学意义（P＜0.05），其中B组T3时点的cTnI值显著高于T1、T2时点（P＜0.05），C组T2时点的cTnI值显著低于T1、T3时点（P＜0.05），而T2、T3时点的cTnI值均显著低于T1时点（P＜0.05）。 ② 3组的ATP、ADP值比较差异有统计学意义（P＜0.05），其中C组的ATP、ADP值均显著高于B组（P＜0.05）。③ 3组的3-KAT水平比较差异有统计学意义（P＜0.05），其中C组的3-KAT水平显著低于B组（P＜0.05）。结论 曲美他嗪可通过抑制心肌线粒体长链3-KAT的活性，提高心肌组织ATP、ADP的含量，改善心肌能量代谢，对ADM化疗诱导的乳腺癌荷瘤裸鼠的心肌损伤具有一定的保护作用。

关键词:  乳腺肿瘤, 曲美他嗪, 阿霉素, 裸鼠, 心肌保护, 能量代谢

Abstract:  Objective To investigate the myocardial protective effects of trimetazidine（TMZ） and its mechanism of action by re-searching the drug′s influence on myocardial energy metabolism after adriamycin（ADM） chemotherapy in a nude mouse breast cancer model. Methods Nude mice（n=27） with breast cancer were randomly divided into three groups：group A（control group） received saline（10 ml/kg） injections into the abdominal cavity，and groups B and C received ADM injections（2.5 ml/kg） into the abdominal cavity twice a week for 4 weeks. From the third week，group C was given TMZ by gavage 20 mg/（kg·d），once a day for 14 days； groups A and B received the same amounts of saline at the same times. Mice were anesthetized on the second day after the last administration.At three time points（before gavage，T1；before anesthesia，T2；30 min afer anesthesia，T3），blood（0.2 ml） and myocardial tissue specimens were taken from mice in all three groups.Serum levels of cTnI and activity of myocardial mitochondrial long-chain 3-ketoacyl coenzyme A thiolase（3-KAT） were measured by enzyme-linked immunosorbent assay（ELISA）.Levels of adenosine triphosphate（ATP） and adenosine diphosphate（ADP） in myocardial tissue were determined by high performance liquid chromatography（HPLC）. Results  ① At T1，serum cTnI level was higher in groups B and C than in group A（P＜0.05），but there was no significant difference between groups B and C（P>0.05）.At T2 and T3，the cTnI level was significantly lower in group C than in group B（P<0.05）.Serum cTnI level in group A did not vary significantly across all three time points（P>0.05）.In group B，in contrast，serum cTnI level was higher at T3 than at T1 and T2（P＜0.05）.In group C，the cTnI level was significantly higher at T1 than at T2 or T3，and T2 was significantly lower than at T1 and T3（P＜0.05）.② ATP and ADP levels were significantly different among the three groups（P＜0.05）；these levels were higher in group C than in group B（P＜0.05）.③ 3-KAT levels were significantly different among the three groups（P＜0.05）；the level was lower in group C than in group B（P＜0.05）. Conclusion  Trimetazidine protects against myocardial injury induced by ADM chemotherapy in a nude mouse breast cancer model.It exerts these protective effects by improving myocardial energy metabolism，inhibiting myocardial mitochondrial 3-KAT activity and improving ATP and ADP levels in myocardial tissue.

Key words: Breast neoplasms, Trimetazidine, Adriamycin, Nude mice, Myocardial protection, Energy metabolism