Study on TCM syndromes of doxorubicin-induced cardiotoxicity mice model

ZHANG Yawen; WANG Xiaoping; LI Weili; WANG Ruochong; LING Guanjing; JIANG Jinchi; CAO Jing; YU Lishuang; CUI Xinyu; WANG Yong

doi:10.3969/j.issn.1006-2157.2023.10.008

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Study on TCM syndromes of doxorubicin-induced cardiotoxicity mice model

Experimental Studies | 更新时间：2023-11-06

- Study on TCM syndromes of doxorubicin-induced cardiotoxicity mice model
- Journal of Beijing University of Traditional Chinese Medicine Vol. 46, Issue 10, Pages: 1374-1381(2023)
- 作者机构：
  
  1.北京中医药大学中医学院　北京　100029
  2.证候与方剂基础研究北京市重点实验室
  3.证候与方剂基础研究教育部重点实验室
- 作者简介：
  
  Prof.WANG Yong, Ph.D., Doctoral Supervisor. School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No.11, Beisanhuan Donglu, Chaoyang District, Beijing 100029. E-mail: doctor_wangyong@163.com
- 基金信息：
  
  National Natural Science Foundation of China(81822049;82174364;81930113;82174364);National Major New Drug Development(2019ZX09201004－001－011)
- DOI：10.3969/j.issn.1006-2157.2023.10.008
  CLC： R241
- Received：28 February 2023，
  
  Online First：11 September 2023，
  
  Published：30 October 2023
- 稿件说明：
移动端阅览
ZHANG Yawen, WANG Xiaoping, LI Weili, et al. Study on TCM syndromes of doxorubicin-induced cardiotoxicity mice model[J]. Journal of Beijing University of Traditional Chinese Medicine, 2023, 46(10): 1374-1381.
DOI：

ZHANG Yawen, WANG Xiaoping, LI Weili, et al. Study on TCM syndromes of doxorubicin-induced cardiotoxicity mice model[J]. Journal of Beijing University of Traditional Chinese Medicine, 2023, 46(10): 1374-1381. DOI： 10.3969/j.issn.1006-2157.2023.10.008.

摘要

目的

通过观测阿霉素诱导的心脏毒性(doxorubicin-induced cardiactoxicity，DIC)小鼠模型的宏观体征和微观指标，建立稳定的DIC病证结合动物模型，探讨DIC小鼠模型中医证候变化规律。

方法

将20只SPF级C57 BL/6野生型小鼠随意分为模型组和正常组，每组10只，模型组小鼠行尾静脉注射阿霉素5 mg/kg，正常组小鼠尾静脉注射生理盐水，1次/周，共注射4周。每次尾静脉注射第2天，观察小鼠一般状况，统计小鼠舌色三原色(RGB)比值、负重力竭游泳时间。采用超声心动检测及病理苏木精－伊红(HE)染色、Masson染色、TUNEL染色进行模型评价。生化法检测小鼠血清乳酸脱氢酶(LDH)、肌酸激酶同工酶(CK-MB)、丙二醛(MDA) 、血清超氧化物歧化酶(SOD)、一氧化氮(NO)及小鼠组织三磷酸腺苷(ATP)含量。

结果

造模第1周，与正常组比较，模型组小鼠精神萎靡，活动喘息加重、活动减少、体质量下降(

0.05)、力竭游泳时间缩短(

0.05)；第2周起，小鼠舌质暗红出现瘀斑，舌质r值降低(

0.01)，g、b值升高(

0.05)。与正常组比较，模型组小鼠LDH 、CK-MB和MDA含量增加(

0.01)，SOD、NO及ATP含量降低(

0.01)。

结论

DIC小鼠模型，宏观体征、证候随时间延长和疾病进展，综合微观血生化及宏观指征结果，DIC小鼠模型1周出现气虚证，2～4周逐渐演变为气虚血瘀证。

Abstract

Objective

Aimed to establish a stable doxorubicin-induced cardiactoxicity (DIC) animal model by observing the macroscopic signs and microscopic indexes of DIC in mice

to establish a stable animal model of DIC combined with disease and syndrome

and to explore the regularity of traditional Chinese medicine(TCM) syndrome changes in DIC mice model.

Methods

SPF grade C57 BL/6 wild-type mice randomly devided into the normal group(

=10) and the model group(10=10)

the model group mice were injected with adriamycin 5 mg/kg by the tail vein injection

and the normal group were injected with normal saline

once a week for 4 weeks. Echocardiography and pathological staining of HE

Masson and TUNEL were used to evaluate the model. The general condition of mice was observed every week

and the RGB value ratio of tongue and exhaustive swimming time bearing weight were recorded. The serum levels of lactate dehydrogenase (LDH)

creatine kinase isoenzyme (CK-MB)

malondialdehyde (MDA)

superoxide dismutase (SOD)

nitric oxide (NO) and tissue adenosine triphosphate (ATP) were detected by biochemical method .

Results

Compared with the normal group

from the first week

the mice in the model group showed listlessness

increased activity wheezing

decreased activity

decreased body weight (

0.01)

and shortened exhaustive swimming time (

0.05). From the 2nd week

the r value of tongue was decreased (

0.01)

while the g value and b value were significantly increased (

0.01). In addition

compared with the normal group

the levels of LDH

CK-MB and MDA in the model group were increased (

0.01)

and the contents of SOD

NO and ATP were decreased (

0.01).

Conclusion

In the DIC mice model

macroscopic signs and syndromes change with time and disease progression. The result of microscopic blood biochemistry and macroscopic signs showed that the DIC mice model appeared qi deficiency syndrome at week 1

and gradually evolved into qi deficiency and blood stasis at week 2-4.

关键词

Keywords

references

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