右雷佐生对非蒽环类肿瘤心脏病的保护作用  

The protective effect of Dexrazoxane on onco-cardiology inducedby anti-cancer agents other than anthracyclines

作　　者：伦静雯 卢宇靖 袁宇玺 黎秋茹 冯启荣 赵海山 LUN Jing-wen;LU Yu-jing;YUAN Yu-xi;LI Qiu-ru;FENG Qi-rong;ZHAO Hai-shan(School of Biomedical and Pharmaceutical Sciences;School of Chemical Engineering and Light Industry,Guangdong University of Technology,Guangzhou 510006,China;Guangdong Academy of Medical Sciences,Guangdong Provincial People′s Hospital,Guangzhou 510080,China)

机构地区：[1]广东工业大学生物医药学院,广东广州510006 [2]广东工业大学轻工化工学院,广东广州510006 [3]广东省人民医院广东省医学科学院,广东广州510080

出　　处：《中国药理学通报》2022年第12期1816-1822,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81903600)。

摘　　要：目的应用斑马鱼胚胎模型评价右雷佐生(dexrazoxane,Dex)对非蒽环类抗肿瘤药物引起的肿瘤心脏病的保护作用,包括顺铂(cisplatin,DDP)、紫杉醇(paclitaxel,Taxol)、硫酸长春新碱(vincristine sulfate,VCR)、5-氟尿嘧啶(5-fluorouracil,5-FU)和环磷酰胺(cyclophosphamide,CTX)。方法选取24 hpf(hours post-fertilization)斑马鱼胚胎暴露于不同浓度的药物中,利用显微镜观察48、72、96 hpf斑马鱼胚胎的存活率和整体动物形态;采用摄像系统测定和计算药物处理48 h后斑马鱼胚胎的心功能指标:心率(heart rate,HR)、心室收缩分数(fractional shortening,FS)、心室容积(stroke volume,SV)、心脏输出量(cardiac output,CO)。通过已建立的非蒽环类肿瘤心脏病模型评价Dex对该模型的保护作用。结果在急性毒性方面,DDP、VCR、5-FU和CTX均明显降低斑马鱼胚胎的存活率,其LC_(50)值分别为437.655、25.538、65.606、19.021 mmol·L^(-1)。除Taxol外,其余4种抗肿瘤药物均出现明显的整体动物形态和心功能指标的改变。在Dex对除蒽环类的4种肿瘤心脏病保护作用研究中,只对DDP具有明显的保护作用,可以改善DDP引起的心脏毒性,且Dex的最佳药效浓度为80μmol·L^(-1)。结论通过建立的DDP、VCR、5-FU和CTX引起药物毒性的斑马鱼模型,证明Dex只对DDP引起的毒性起保护作用。Aim To evaluate the protective effect of Dexrazoxane(Dex)on onco-cardiology caused by chemotherapeutic drugs other than anthracycline antitumor drugs using zebrafish embryos,including:cisplatin,paclitaxel,vincristine sulfate,5-fluorouracil and cyclophosphamide.Methods Zebrafish embryos at 24 hpf(hours post-fertilization)were exposed to different concentrations of drugs.The survival rate and the overall animal morphology at 48 hpf,72 hpf and 96 hpf were observed with a microscope.Heart rate,ventricular contraction fraction,ventricular volume,and cardiac output were measured and calculated by video recordings made with a VCD system.The protective effect of Dex was evaluated using the established model of onco-cardiology induced by anti-tumor drugs other than anthracyclines.Results In terms of acute toxicity,cisplatin,vincristine sulfate,5-fluorouracil and cyclophosphamide all significantly reduced the survival rate of zebrafish embryos.The LC_(50) value was 437.655,25.538,65.606 and 19.021 mmol·L^(-1),respectively.In addition to paclitaxel,the other four anti-tumor drugs all showed significant changes in overall animal morphology and cardiac function indicators.In the study of the protective effect of Dex on four kinds of tumor heart diseases except anthracyclines,only cisplatin had a significant protective effect,which could improve the cardiotoxicity caused by cisplatin.The optimal concentration of Dex was 80μmol·L^(-1).Conclusions Zebrafish models of drug toxicity caused by cisplatin,vincristine sulfate,5-fluorouracil,and cyclophosphamide is established,which proves that Dex only has a protective effect on the toxicity caused by cisplatin.

关 键 词：斑马鱼 非蒽环类抗肿瘤药物 右雷佐生 肿瘤心脏病 急性毒性 组织器官毒性 心功能指标 

分 类 号：R-332[医药卫生] R322.1R541R730.5R979.1