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Suppl. Mater.: 

CLC number: R542.2

On-line Access: 2016-12-05

Received: 2016-06-08

Revision Accepted: 2016-08-19

Crosschecked: 2016-11-10

Cited: 0

Clicked: 1517

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Li-juan Shen

http://orcid.org/0000-0001-6401-3220

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Journal of Zhejiang University SCIENCE B 2016 Vol.17 No.12 P.975-983

http://doi.org/10.1631/jzus.B1600257


Developing a rat model of dilated cardiomyopathy with improved survival


Author(s):  Li-juan Shen, Shu Lu, Yong-hua Zhou, Lan Li, Qing-min Xing, Yong-liang Xu

Affiliation(s):  Wuxi Hospital of Traditional Chinese Medicine, Wuxi Hospital Affiliated to Nanjing University of Chinese Medicine, Wuxi 214071, China; more

Corresponding email(s):   Panda55007@163.com, toxo2001@163.com

Key Words:  Doxorubicin, Dilated cardiomyopathy, Animal model, 18FDG-PET


Li-juan Shen, Shu Lu, Yong-hua Zhou, Lan Li, Qing-min Xing, Yong-liang Xu. Developing a rat model of dilated cardiomyopathy with improved survival[J]. Journal of Zhejiang University Science B, 2016, 17(12): 975-983.

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author="Li-juan Shen, Shu Lu, Yong-hua Zhou, Lan Li, Qing-min Xing, Yong-liang Xu",
journal="Journal of Zhejiang University Science B",
volume="17",
number="12",
pages="975-983",
year="2016",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1600257"
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%T Developing a rat model of dilated cardiomyopathy with improved survival
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%A Shu Lu
%A Yong-hua Zhou
%A Lan Li
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T1 - Developing a rat model of dilated cardiomyopathy with improved survival
A1 - Li-juan Shen
A1 - Shu Lu
A1 - Yong-hua Zhou
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DOI - 10.1631/jzus.B1600257


Abstract: 
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.

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 mRNA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 mRNA水平、心肌病理变化及18FDG-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。

关键词:阿霉素;扩张型心肌病;动物模型;18FDG-PET

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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[38]Fig. S1 Myocardial metabolism imaging by 18FDG-PET/CT

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