Effect of Modified Xiongxiesan on Proliferation of Airway Smooth Muscle Tissues and Expressions of MMP-9 and TIMP1 in CVA Model Rats / 中国实验方剂学杂志

ABSTRACT

Objective:To explore the effect of modified Xiongxiesan on the proliferation of airway smooth muscle tissues and the expressions of matrix metalloproteinase-9（MMP-9）， tissue inhibitor of metalloproteinase-1 （TIMP-1） in cough variant asthma （CVA） model rats. Method:A total 48 male SD rats were randomly divided into the normal control group （8 rats） and model group （40 rats）. CVA model of rats were established through the intraperitoneal administration with 2 mg ovalbumin （OVA） and 100 mg Al（OH）3， and then aerosol inhalation of 1％ OVA 15 days later. The same volume of sterile saline was given to the normal group through the intraperitoneal injection. Then 40 rats in the modeling group were randomly divided into model group， modified Xiongxiesan group （TCM group， 6 g·kg-1·d-1）， montelukast group （0.4 mg·kg-1·d-1）， chemokine receptor1/2 （CXCR1/2） inhibitor group （G31P group injected subcutaneously via the neck with a dose of 0.5 mg·kg-1 every other day）， and CXCR1/2 inhibitor and modified Xiongxiesan group （G31P+TCM group）， with 8 rats in each group. The control group and the model group were orally given distilled water 10 mL·kg-1·d-1. Then the rats were sacrificed， and lung samples were collected. Histological changes were examined by hematoxylin-eosin（HE）. Basement membrane perimeter （PBM），wall area of bronchial tube （WAt），wall area of bronchial smooth muscle （WAm） and the number of smooth muscle cells （N） were measured using image pro-plus software and standardized based on PBM. The expressions of PCNA， MMP9 and TIMP1 were detected by immunohistochemistry. Result:Compared with the control group， there were a large number of inflammatory cells infiltration and moderate hyperplasia of smooth muscle area in the model group， which however were alleviated in other groups. The expressions of PCNA and MMP-9，TIMP1 were higher in the model group，which were reduced in other groups significantly. Conclusion:Modified Xiongxiesan can reduce the thickness of airway smooth muscle tissue in the CVA model rats， which may be correlated with the inhibition of the CXCR1/2 pathway， thereby reducing the proliferative activity of smooth muscle tissue and inhibiting the expression of related matrix metalloproteinases.