吗丙嗪对阿霉素心脏毒性的防治作用

PREVENTIVE EFFECT OF PROBIMANE ON THE CARDIOTOXICITY INDUCED BY DOXORUBICIN IN MICE

阿霉素是临床上常用的抗肿瘤药物,治疗范围广,但毒副作用大,心脏毒性是限制其临床应用的主要不良反应。各国药理学家从不同角度研究阿霉素心脏毒性的防治方法。我们发现,阿霉素连续给药,小鼠心、肝、脾、胸腺及肾等脏器的重量明显下降,预先给予吗丙嗪上述脏器重量有所回升,其中以心、睥、胸腺增重较为明显。光学显微镜检查可见,10只动物中有4例出现“Ⅲ”级病变,6例为“Ⅱ”级病变,吗丙嗪与阿霉素合用组10只小鼠中,4例为正常心肌,无任何病变,4例为“Ⅰ”级病变,2例为“Ⅱ级心肌病变,无1例为“Ⅲ级”病变,经 Ridit 分析,组间差异显著(P<0.05)。电镜检查可见,单用阿霉素组小鼠心肌出现大量变性心肌细胞,核异染色质增多,胞浆内大面积肌原纤维断裂,溶解;线粒体肿胀,嵴断裂,溶解及空泡比,预先给予吗丙嗪,阿霉素所致心肌病变明显减轻。

Doxorubicin,an anthracycline antibiotic,is broad-spectrum antitumor agent,but its clinical use is limited by its cardiotoxicity.To search for the cardio-protective drug is the main task for pharmacologist.It is found that probimane,a bisdioxopiperazine compound,could reverse the reduction in heart weight in mice treated with doxorubicin.Light microscopically.DOX could cause heart tissue damage showing score 3 pathological changes with large area of atrophic changes in myofibrillae in 4 of 10 mice.There was no score 3 pathological changes of heart muscle in mice treated with DOX and probimane.Electron microscopically,the atrophic changes of myofibrillae.disorderly arrangement of myofilaments,swelling and vacuolization of mitochondria were noted with doxorubicin alone.Marked reduction in the severity of myocardiopathy in mice treated with doxorubicin and probimane.From the data obtained.it is suggested that probimane could ameliorate the cardio-toxicity induced by doxoru bicin.