Objective

2

To discuss the establishment method of disease and syndrome-integrated animal model of chronic cough with cold fluid retained in the lung

and evaluate its reliability.

Methods

2

48 male SPF guinea pigs were randomly divided into the normal control group

the cough model group

the cold body and diet group

and disease syndrome combination model group (

n

=12 in each group). The cough hypersensitivity animal model of was established by ovalbumin(OVA)

while the traditional Chinese medicine (TCM) syndrome model of cold fluid retained in the lung was established by cold body and cold drink stimulation. Therefore

the disease and syndrome combination animal model of chronic cough with cold fluid retained in the lung was established by combining the above two methods. The general state and behaviors

cough frequency

airway resistance

lung pathology

the mRNA expression of lung transient receptor potential ankyrin A1(hereafter TRPA1)

substance P(hereafter SP)

calcitonin gene-related peptide(hereafter CGRP) and the protein expression of lung TRPA1

neurokinin-1 receptor (hereafter NK-1R) and CGRP were observed and measured.

Results

2

As compared with the normal control group and the cough model group

symptoms of chronic cough with cold fluid retained in the lung including the general state and behaviors of the guinea pigs were more obvious in the cold body and diet group and especially in the disease syndrome combination model group. As compared with the normal control group

the cough frequency

airway resistance

the mRNA expression of lung TRPA1

SP and CGRP

the protein expression of lung TRPA1

NK-1R and CGRP were all elevated in the cough model group and the disease syndrome combination model group (

P

<

0.01)

and the protein expression of lung TRPA1 was significantly increased in the cold body and diet group (

P

<

0.01). As compared with the cough model group

cough frequency

airway resistance

the mRNA expression of lung TRPA1

SP and CGRP

the protein expression of lung TRPA1

NK-1R and CGRP were all significantly decreased in the cold body and diet group(

P

<

0.01) and significantly increased in the disease syndrome combination model group(

P

<

0.01 or

P

<

0.05). As compared with cold body and diet group

cough frequency

airway resistance

the mRNA expression of lung TRPA1

SP and CGRP

the protein expression of lung TRPA1

NK-1R and CGRP were all significantly increased in the disease syndrome combination model group(

P

<

0.01 or

P

<

0.05). As compared with the normal control group

lung pathology showed apparent structural destruction and tissue inflammation in the other three groups. The pathological severity from low to high were the cold body and diet group

the cough model group and the disease syndrome model.

Conclusions

2

The disease and syndrome combination animal model of chronic cough with cold fluid retained in the lung could be successfully established by the TCM and Western interventions. This model not only conforms to the pathogenesis of Western medicine

but also reflects the characteristics of TCM syndromes. It can provide a reliable model basis for the study of the mechanism of chronic cough and the pharmacodynamics in TCM.