曲妥珠单抗对心肌细胞损害作用的实验研究  

Experimental study on the effect of trastuzumab on the damage of myocardial cells

作　　者：刘卫东[1] 叶英响[1] 杨洁红 

机构地区：[1]浙江省义乌市中心医院药剂科,浙江义乌322000 [2]浙江中医药大学基础医学院,杭州310053

出　　处：《实用药物与临床》2015年第5期532-535,共4页Practical Pharmacy and Clinical Remedies

基　　金：国家自然科学基金(81073139)

摘　　要：目的探讨曲妥珠单抗对大鼠心功能的影响及其作用机制。方法 50只6周龄SPF级SD大鼠随机均分为观察组和对照组。观察组大鼠腹腔注射曲妥珠单抗,共计给药7 d;对照组大鼠腹腔注射生理盐水,体积与注射时间同观察组。分别于给药前后用心脏超声检查大鼠心功能变化;采用TUNEL技术检测细胞凋亡情况,同时检测大鼠心肌细胞Caspase-3活性。结果给药1周后,观察组大鼠LVEDd、LVESd显著扩大,LVPWDd、LVPWSd明显变薄,LVEF、LVFS显著降低,与对照组比较差异有统计学意义(P<0.05)。给药1周后,观察组凋亡指数(AI)显著增加,Caspase-3活性显著增强,与对照组比较差异有统计学意义(P<0.05)。结论曲妥珠单抗会导致心肌细胞损害,其机制可能与激活Caspase-3、促进心肌细胞凋亡有关。Objective To explore the effects and mechanism of trastuzumab on cardiac function of rats. Methods 50 SD rats were randomly divided into observation group （n=25） and control group （n=25）,rats in observation group were injected with trastuzumab for 7 d; rats in control group were intraperitoneally injected with physiological saline,with the same volume and injection time as observation group. The cardiac function was detected by cardiac ultrasonography before and after injection,TUNEL technique was used to determine the cell apoptosis,and the myocardial cell Caspase-3 activity was detected. Results The LVEDd,LVESd of rats in observation group signifi-cantly expanded at 1 weeks after administration, and the LVPWDd, LVPWSd were significantly thinner, LVEF and LVFS significantly reduced,there were significant differences between the two groups （P〈0. 05）. The apoptosis index of observation group increased,and the Caspase-3 activity enhanced（P〈0. 05）. Conclusion Trastuzumab can lead to myocardial cell damage,and the mechanism may be related to the activation of Caspase-3 and promoting myocardial cell apoptosis.

关 键 词：曲妥珠单克隆抗体 心功能 凋亡 

分 类 号：R965[医药卫生—药理学]