提高扩张型心肌病动物模型的生存率
目的:比较在腹腔注射相同剂量阿霉素(12 mg/kg)下,不同给药方案构建扩张型心肌病大鼠模型的生存率。创新点:首次应用腹腔注射阿霉素1 mg/kg,一周两次的方法构建扩张型心肌病大鼠模型,并与常规的方法进行生存率的比较。方法:将150只SD雄鼠分为对照组(腹腔注射生理盐水)、Dox 1组(腹腔注射阿霉素1 mg/kg一周两次,共六周)和Dox 2组(腹腔注射阿霉素2 mg/kg一周一次,共六周)。观察及比较各组大鼠的体重、生存率、心腔大小、pro-BNP、CRP、CREA、AST和Caspase-3 mR NA水平。观察各组大鼠心肌病理变化,同时进行^18FDG-PET心肌代谢显像。结论:本...
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Published in | 浙江大学学报:B卷英文版 Vol. 17; no. 12; pp. 975 - 983 |
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Main Author | |
Format | Journal Article |
Language | English |
Published |
2016
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Subjects | |
Online Access | Get full text |
ISSN | 1673-1581 1862-1783 |
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Summary: | 目的:比较在腹腔注射相同剂量阿霉素(12 mg/kg)下,不同给药方案构建扩张型心肌病大鼠模型的生存率。创新点:首次应用腹腔注射阿霉素1 mg/kg,一周两次的方法构建扩张型心肌病大鼠模型,并与常规的方法进行生存率的比较。方法:将150只SD雄鼠分为对照组(腹腔注射生理盐水)、Dox 1组(腹腔注射阿霉素1 mg/kg一周两次,共六周)和Dox 2组(腹腔注射阿霉素2 mg/kg一周一次,共六周)。观察及比较各组大鼠的体重、生存率、心腔大小、pro-BNP、CRP、CREA、AST和Caspase-3 mR NA水平。观察各组大鼠心肌病理变化,同时进行^18FDG-PET心肌代谢显像。结论:本实验中结果显示,Dox 1组和Dox 2组在pro-BNP、Caspase-3 mR NA水平、心肌病理变化及^18)FDG-PET心肌代谢显像上均没有明显差异;但Dox 1组的生存率是78%,而Dox 2组的生存率是52%;同时,Dox 2组大鼠的血清CREA、AST和CRP水平比Dox 1组明显升高。综上所述,腹腔注射阿霉素1 mg/kg一周两次的方法在成功构建扩张型心肌病大鼠模型的同时大大提高了存活率。 |
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Bibliography: | Doxorubicin; Dilated cardiomyopathy; Animal model; ^18FDG-PET 33-1356/Q To compare the continuous infusion and intermittent bolus injection administration protocols of doxorubicin(Dox) under the same cumulative dose(12 mg/kg), and establish a rat dilated cardiomyopathy model with improved survival, a total of 150 Sprague-Dawley(SD) rats were divided into three groups: a control group, administered with normal saline; a Dox 1 group, administration twice a week at 1 mg/kg; a Dox 2, administration once a week at 2 mg/kg. Mortality rates in the Dox 1 and Dox 2 groups were 22% and 48%, respectively(P〈0.05). As shown by echocardiography, both Dox groups exhibited significant chamber dilatation and reduced cardiac function(all P〈0.05 vs. control). Plasma brain natriuretic peptide and C-reactive protein concentrations were significantly increased(P〈0.05) with both Dox regimens. The concentrations of Caspase-3 in myocardial tissues of rats significantly increased in both doxorubicin regimens. Myocardial metabolism imaging by histology and ^18F-fluoro-deoxyglucose-positron emission tomography(^18FDG-PET) both revealed decreased myocardial viability and necrosis, and even interstitial fibrosis, in left ventricles(LVs) in both Dox groups. Serum creatinine and aspartate aminotransferase concentrations were significantly higher in the Dox 2 model than in the Dox 1 model. Doxorubicin given at both regimens induced dilated cardiomyopathy, while its administration at lower doses with more frequent infusions reduced the mortality rate. |
ISSN: | 1673-1581 1862-1783 |