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金翠柳,柴 钰,凌 望,吴美平,金素安.多柔比星致小鼠慢性心脏毒性模型的构建及评估[J].中国比较医学杂志,2022,32(4):14~21.
多柔比星致小鼠慢性心脏毒性模型的构建及评估
Construction and evaluation of a doxorubicin-induced chronic cardiotoxicity mouse model
投稿时间:2021-03-06  
DOI:10. 3969 / j.issn.1671-7856. 2022. 04. 003
中文关键词:  多柔比星  动物模型  小鼠  慢性心脏毒性
英文关键词:doxorubicin  animal model  mouse  chronic cardiac toxicity
基金项目:
作者单位E-mail
金翠柳 上海中医药大学附属市中医医院,上海 200071 954700668@ qq.com 
柴 钰 上海中医药大学附属市中医医院,上海 200071  
凌 望 上海中医药大学附属市中医医院,上海 200071  
吴美平 上海中医药大学附属市中医医院,上海 200071  
金素安 上海中医药大学,上海 201203 zhongyaojin@ 126.com 
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中文摘要:
       目的 基于病理变化评估不同浓度多柔比星致小鼠心脏毒性模型的成模效果。 方法 采用 8 周龄 SPF 级雄性 C57BL/ 6J 小鼠 36 只,随机分为生理盐水组(NS 组)、3 mg / kg 多柔比星组、4 mg / kg 多柔比星组、5 mg / kg 多柔比星组、6 mg / kg 多柔比星组、7 mg / kg 多柔比星组,每组 6 只。 采用腹腔注射的给药方式,每 3 d 1 次,共 10 次,观察小鼠的状态,对小鼠心重、体重、心重比、心胫比、生存情况进行统计,并检测心脏组织中凋亡蛋白的表达情况以及心肌纤维化程度,心脏中段横截面积与单个心肌细胞横截面积大小等来评价多柔比星诱导的小鼠慢性心脏 毒性模型。 结果 统计整个实验周期中小鼠的生存情况,3~ 5 mg / kg 各给药组小鼠均存活 6 只,生存率为 100%,6 mg / kg 给药组小鼠存活 5 只,生存率为 83. 3%,7 mg / kg 给药组小鼠存活 1 只,生存率约达 16. 7%。 与 NS 组相比, 给药组小鼠的生存率呈下降趋势,且与多柔比星给药浓度呈负相关,而小鼠的心重、体重、心胫比则呈剂量依赖性下降。 当多柔比星浓度达到 4 mg / kg 时,相较 NS 组,模型组小鼠心肌细胞凋亡比例增加,心肌纤维化面积增多,且发现心脏整体缩小,心肌细胞横截面积相应缩小,有统计学差异(P<0. 05)。 结论 小鼠心脏纤维化、心肌细胞凋亡、萎缩及生存率等指标随着体内多柔比星蓄积量增加而恶化,造模时选用 4 ~ 6 mg / kg 浓度的多柔比星构建小鼠慢性心脏毒性模型较为合适,超过该剂量则小鼠死亡率较高,不利于后期实验。
英文摘要:
       Objective To evaluate the effect of different levels of doxorubicin-induced cardiotoxicity in mice by examining pathological changes. Methods In total, 36 male C57BL/ 6J mice (8 weeks old, SPF grade) were randomly assigned to the normal saline group ( NS group), 3 mg / kg doxorubicin group, 4 mg / kg doxorubicin group, 5 mg / kg doxorubicin group, 6 mg / kg doxorubicin group and 7 mg / kg doxorubicin group ( 6 mice in each group). Mice received intraperitoneal injection of saline or different concentrations of doxorubicin, 3 days/ times, 10 times in total. We monitored heart weight, body weight, ratio of body weight with heart weight, tibia to heart weight ratio, survival rate and evaluated cardiomyocyte apoptosis and cardiac fibrosis, simultaneously measured the cross-sectional area of heart and single myocyte cross-sectional area size. Results All six mice in each of the 3~ 5 mg / kg groups survived, with a survival rate of 100%. Five mice in the 6 mg / kg group survived, the survival rate was approximately 83. 3%. One mouse in the 7 mg / kg group survived, the survival rate was approximately 16. 7%. The survival rate of mice in the treatment groups decreased and was negatively correlated with doxorubicin concentration. The heart weight, body weight and heart to tibia ratio of mice in the treatment groups decreased in a dose-dependent manner. When the concentration of doxorubicin reached 4 mg / kg, the proportion of cardiomyocyte apoptosis increased, the area of myocardial fibrosis increased, and the cross-sectional area of the whole heart and cardiomyocyte decreased in the model groups compared with the NS group, and these differences were statistically significant (P<0. 05). Conclusions The indexes of cardiac fibrosis, cardiomyocyte apoptosis, atrophy and survival rate of mice worsen with the increase of doxorubicin accumulation in vivo. A concentration of 4 ~ 6 mg / kg doxorubicin is appropriate to build the model of chronic cardiotoxicity in mice, if doxorubicin exceeds this dose, the death rate of mice will be high, which is not conducive to the later experiment.
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