多柔比星对新西兰大白兔心功能及心肌血管紧张素Ⅱ水平的影响  

Effects of doxorubicin on changes of cardiac function and angiotensin Ⅱ level in myocardium of New Zealand white rabbits

作　　者：张辉[1] 郑荣琴[1] 钱孝贤[2] 郝宝顺[2] 张成喜[2] 

机构地区：[1]中山大学附属第三医院超声科,中山大学超声与介入治疗研究所,广东广州510630 [2]中山大学附属第三医院心内科,广东广州510630

出　　处：《中国药理学与毒理学杂志》2014年第4期497-502,共6页Chinese Journal of Pharmacology and Toxicology

基　　金：广东省科技计划基金资助项目(2011B061300005)~~

摘　　要：目的研究多柔比星对兔的心肌毒性作用及其机制。方法雄性健康新西兰大白兔静脉注射多柔比星2 mg·kg-1,每周1次,连续8周,分别于给药前、给药期间及停药后8周内每隔7 d采用超声检测射血分数和心导管检测左心室压力最大上升速率(+dp/dtmax),HE染色及透射电镜观察心肌组织形态及心肌细胞超微结构,TUNEL法测定凋亡指数,Western蛋白质印迹法测定血管紧张素Ⅱ(AngⅡ)水平。结果给药7次后,射血分数明显下降(P<0.05),8次后下降至谷底;给药3次后,+dp/dtmax明显降低(P<0.05),8次后的第1周时达到最低,之后逐步上升,停药后第6周不再出现明显上升,但未恢复至正常水平。给药2次后,心肌AngⅡ水平明显增加(P<0.05),停药后的第1周最高,之后逐步下降,停药后第6周不再出现明显降低,但是未降低至给药前的水平。给药1次心肌凋亡指数明显增加(P<0.05),停药后的第1周达到高峰,之后逐步下降,停药后第5周末不再出现明显降低,但是数值仍然高于给药前。结论多柔比星毒性可导致兔心肌AngⅡ水平升高,继而可通过活性氧和钙离子失衡诱导心肌结构进一步破坏和心室重构。OBJECTlVE To investigate the myocardial toxicity of doxorubicin on the myocardium of rabbits and mechanism. METHODS Doxorubicin 2 mg·kg-1 was injected once a week for eight weeks. After discontinuation of doxorubicin,observation was performed for another 8 weeks. Every weekend,＆amp;nbsp;ultrasound examination,cardiac catheterization,angiotensinⅡ（AngⅡ）Western blotting and pathoIogi-cal examination were performed to analyze eject fraction（ EF）,maximal rate of rise of Ieft ventricular pressure（＋dp/ dtmax ）,AngⅡexpression Ievel,apoptosis index（AI）and the structure of the myocardium. RESULTS At the 7th injection,EF decreased（ P ﹤0.05）,but reached the bottom value at the 8th injection. At the 3rd injection,Ieft ventricular ＋dp/ dtmax decreased（ P ﹤0.05）and reached the bottom value one week after withdrawal. After that,it increased and reached a high value six weeks after withd-rowal. But it was still Iower than before administration. At the 2nd injection,AngⅡ expression increased （P﹤0.05）. At 1 week after withdrawal,it reached the top value,but than decreased and reached a Iow value six weeks after withdrowal,but was still higher than before administration. At the 1st injection,AI increased（ P ﹤ 0.05）. At 1 week after withdrawal,it reached the top value,but then decreased and reached a Iow value 5 weeks after withdrawal. But it was still higher than before administration. CONCLUSlON Doxorubicin cardiac toxicity can induce an elevated Ievel of myocardial AngⅡ,possibly associated with increased aldosterone and myocardial tension. Increased Ang Ⅱ may induce further myocardial structural damage and ventricular remodeling through the ROS and calcium imbalance.

关 键 词：血管紧张素 多柔比星 心脏毒性 

分 类 号：R445.1[医药卫生—影像医学与核医学] R965[医药卫生—诊断学]