Construction of an animal model combining disease with syndrome of attention deficit hyperactivity disorder with yin deficiency and yang hyperactivity syndrome

WU Yonghong; TIAN Jiao; OU Wenjing; GUO Meizhu; HUANG Xiyan; ZHANG Shuofeng

doi:10.3969/j.issn.1006-2157.2023.05.011

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Construction of an animal model combining disease with syndrome of attention deficit hyperactivity disorder with yin deficiency and yang hyperactivity syndrome

Experimental Studies | 更新时间：2023-06-05

- Construction of an animal model combining disease with syndrome of attention deficit hyperactivity disorder with yin deficiency and yang hyperactivity syndrome
- Journal of Beijing University of Traditional Chinese Medicine Vol. 46, Issue 5, Pages: 657-664(2023)
- 作者机构：
  
  北京中医药大学中药学院　北京　102488
- 作者简介：
  
  Prof. ZHANG Shuofeng, Ph.D., Doctoral Supervisor. School of Chinese Materia Medica, Beijing University of Chinese Medicine, Intersection of Yangguang South Street and Baiyang East Road, Fangshan District, Beijing 102488. E-mail: shuofengzhang@sina.com
- 基金信息：
  
  National Natural Science Foundation of China(81973492)
- DOI：10.3969/j.issn.1006-2157.2023.05.011
  CLC： R272
- Received：20 September 2022，
  
  Online First：22 March 2023，
  
  Published：30 May 2023
- 稿件说明：
移动端阅览
WU Yonghong, TIAN Jiao, OU Wenjing, et al. Construction of an animal model combining disease with syndrome of attention deficit hyperactivity disorder with yin deficiency and yang hyperactivity syndrome[J]. Journal of Beijing University of Traditional Chinese Medicine, 2023, 46(5): 657-664.
DOI：

WU Yonghong, TIAN Jiao, OU Wenjing, et al. Construction of an animal model combining disease with syndrome of attention deficit hyperactivity disorder with yin deficiency and yang hyperactivity syndrome[J]. Journal of Beijing University of Traditional Chinese Medicine, 2023, 46(5): 657-664. DOI： 10.3969/j.issn.1006-2157.2023.05.011.

摘要

目的

构建儿童注意缺陷多动障碍阴虚阳亢证的病证结合动物模型，以促进治疗注意缺陷多动障碍的新药研发。

方法

采用幼龄自发性高血压大鼠(SHR)作为注意缺陷多动障碍模型，将32只SHR按体质量随机分为SHR组、模型组、小儿黄龙颗粒低剂量组(1.88 g/kg)、小儿黄龙颗粒高剂量组(3.75 g/kg)组，另设正常高血压(WKY)组、Wistar组，每组8只。模型组及小儿黄龙颗粒高、低剂量组大鼠每日皮下注射左旋甲状腺素钠(0.3 μg/g)，其余各组大鼠皮下注射生理盐水，连续14 d；从第11天开始，小儿黄龙颗粒高、低剂量组大鼠灌胃相应药物，其余各组灌胃等量生理盐水，连续21 d。观察各组大鼠的饮食量、饮水量、便量、尿量、心率、呼吸频率，以及舌象红色向量(R)、绿色向量(G)、蓝色向量(B)的具体值，上述指标作为阴虚阳亢证的评价指标；观察各组大鼠的自主活动程度、社交偏好程度、注意定势转移能力、易激惹程度，上述指标作为注意缺陷多动障碍行为学评价指标。

结果

与模型组比较，其余各组大鼠心率降低(

0.05)，SHR组及小儿黄龙颗粒高剂量组大鼠呼吸频率降低(

0.05，

0.01)，WKY组及小儿黄龙颗粒高剂量组大鼠舌象G、B值下降(

0.05)。自主活动测试显示，除中心区域停留时间外，模型组其余各指标均高于WKY组(

0.05)，中心区域路程高于SHR组(

0.05)；社交偏好实验显示，模型组与Wistar组比较在陌生鼠侧时间及陌生鼠侧的时间比均减少(

0.01)；注意定势转移测试显示，小儿黄龙颗粒低剂量组较模型组在外维度转换反向学习阶段错误率降低(

0.05)；激惹实验显示，模型组攻击行为总次数较WKY组增加(

0.05)。

结论

采用幼龄SHR皮下注射左旋甲状腺素钠的方式，能够得到稳定、可靠的注意缺陷多动障碍阴虚阳亢证的病证结合动物模型。

Abstract

Objective

We aimed to construct an animal model of combining disease with syndrome of yin deficiency and yang hyperactivity with attention deficit hyperactivity disorder (ADHD) in children

so as to promote the development of new drugs for the treatment of ADHD.

Methods

Young spontaneously hypertensive rats (SHR) were used as ADHD model rats. SHR were randomly divided into four groups according to body mass(

=8): the SHR group

the model group

the

Xiaoer Huanglong

Granule low dose (XEHL-L) group (1.88 g/kg) and the

Xiaoer Huanglong

Granule high dose (XEHL-H) group (3.75 g/kg). The WKY group and the Wistar group were also set up (

=8). Rats in the model group

the XEHL-L group and the XEHL-H group were subcutaneously injected with levothyroxine sodium (0.3 μg/g) daily for 14 days

and rats in the other groups were subcutaneously injected with normal saline. From the 11th day

rats in the XEHL-L group and the XEHL-H group were given drugs by gavage for 21 days

and rats in the other groups were given normal saline by gavage. The diet volume

water volume

defecation volume

urine volume

heart rate

respiratory rate

and specific values of the tongue image red vector (R)

green vector (G) and blue vector (B) were used as evaluation indicators of the syndrome of yin deficiency and yang hyperactivity. The degree of autonomous activity

the degree of social preference

the ability of attention set transfer and the degree of irritability were used as the behavioral indexes of ADHD to evaluate the model.

Results

Compared with the model group

the heart rate of rats in the other groups was decreased (

0.05)

the respiratory rate of rats in the SHR group and the XEHL-H group was decreased (

0.05

0.01)

and the G and B values of tongue images of rats in the WKY group and the XEHL-H group were decreased (

0.05). The degree of autonomic activity showed that except for the central area residence time

all indexes in the model group were higher than those in the WKY group (

0.05)

and the distance in the central region was higher than that in the SHR group (

0.05). The degree of social preference showed that compared with the Wistar group

rats in the model group spent less time with strangers and the ratio of time with strangers was lower (

0.01). The attention set transfer ability test showed that the error rate in the EDS reverse learning stage was lower in the XEHL-L group than in the model group (

0.05). The irritation experiment showed that the aggressive behavior in the model group was increased compared with that in the WKY group (

0.05).

Conclusion

A more stable and reliable model of ADHD syndrome with yin deficiency and yang hyperactivity can be obtained by injecting young SHR with levothyroxine sodium.

关键词

Keywords

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