Objective

2

To explore the effect of Yifei Huatan decoction on relieving airway hyperviscosity in asthmatic rats with spleen deficiency syndrome and its mechanism.

Method

2

Fifty-five SPF level SD rats at 8-9 week of age were used to induce asthma with spleen deficiency syndrome by animal modeling of traditional Chinese medicine combined with asthma of western medicine. After successful modeling， the rats were divided into model group， dexamethasone group， low， medium， and high-dose Yifei Huatan decoction groups by random number table method， and 11 clean SD rats at 8-9 week of age were recorded as a normal group. Rats in the dexamethasone group were given 0.087 5 mg kg

-1

dexamethasone acetate by gavage. Rats in the low， medium， and high-dose Yifei Huatan decoction groups were given 0.8， 1.6， 3.2 g kg

-1

Yifei Huatan decoction liquid extract by gavage， respectively. Rats in the model group and the normal group were given 10 mL kg

-1

distilled water. The medicine were given once per day for 8 w， and the general situation of each group was observed. The levels of interleukin-4 （IL-4）， IL-13， and interferon-

γ

（IFN-

γ

） in bronchoalveolar lavage fluid （BALF） were determined by enzyme-linked immunosorbent assay （ELISA）. The pathological changes in lung tissues of rats were observed by hematoxylin-eosin （HE） staining. Alcian blue-periodic acid Schiff （AB-PAS） staining was used to detect the hyperplasia of airway goblet cells and mucus secretion in rats. The mRNA expressions of transforming growth factor-

β

1

（TGF-

β

1

）， Smad2， Smad3， mucin 5AC （MUC5AC）， and mucin 5B （MUC5B） in the lung tissues of rats were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expressions of TGF-

β

1

， Smad2， Smad3， MUC5AC， and MUC5B in the lung tissues of rats were detected by Western blot.

Result

2

As compared with the normal group， rats in the model group showed the symptoms of spleen deficiency syndrome， such as decreased body weight， muscle emaciation， decreased food intake， increased water intake， increased anal temperature， tiredness， and decreased swimming endurance， accompanied by dyspnea symptoms such as wheezing and nodding. As compared with the normal group， IL-4 and IL-13 levels in the BALF of the model group were significantly increased （

P

<

0.01）， while the IFN-

γ

level was significantly decreased （

P

<

0.01）. In the model group， a large number of inflammatory cells were observed in the mucosa and submucosa of the airway， and the smooth muscle of the trachea was significantly thickened. The hyperplasia， deformation， and exfoliation of various epithelial cells were observed in the mucosa， and the pathological scores of lung tissue increased significantly （

P

<

0.01） in the model group. A large number of goblet cells were observed in the airway with the formation of plenty of mucous thrombus in the model group， and the positive relative staining area of airway， and mRNA and protein expressions of TGF-

β

1

， Smad2， Smad3， MUC5AC， and MUC5B were significantly increased （

P

<

0.01）. As compared with the model group， IL-4 and IL-13 levels in BALF of the dexamethasone group and the Yifei Huatan decoction groups decreased， while the IFN-

γ

level increased. The inflammatory cell infiltration in airway mucosa and submucosa， the thickening of tracheal smooth muscle， the hyperplasia， deformation， and exfoliation of epithelial cells in mucosa were gradually decreased， and the pathological scores of lung tissues decreased significantly （

P

<

0.01） in the dexamethasone group and the Yifei Huatan decoction groups. Goblet cell proliferation gradually decreased， and the positive relative staining area of airway， and mRNA and protein relative expressions of TGF-

β

1

， Smad2， Smad3， MUC5AC， and MUC5B decreased with statistically significant difference （

P

<

0.05，

P

<

0.01）. There was no significant difference in the above indexes in the dexamethasone group and the Yifei Huatan decoction low-dose group. The above indexes were dose-dependent in the low， medium， and high-dose Yifei Huatan decoction groups.

Conclusion

2

Yifei Huatan decoction reduces airway hyperviscosity in asthmatic rats with spleen deficiency syndrome， which may be related to the inhibition of TGF-

β

1

， Smad2， Smad3， MUC5AC， and MUC5B expressions， down-regulation of IL-4 and IL-13 levels， and up-regulation of IFN-

γ

level.