| Airway remodeling is characterized by smooth muscle hyperplasia, mucus glands hypertrophy, subepithelial fibrosis, angiogenesis and change of extracellular matrix and associated with the long term decline in lung function, irreversible airflow obstruction, low airway elasticity and hyperresponsiveness. Airway remodeling is the main physiological change in Asthma and COPD. Preventing and treating airway remodeling can delay the development of the airflow obstruction. The rat model of airway fibrosis is established by intratrachea instilling LPS twice at 14 days interval, then is intervened by Fu-Fang-Bie-Jia-Ruan-Gan-Fang to observe the effect of herbal formula and elucidate its mechanism on airway remodeling intervention at cellular, subcellular and molecular levels. Methods1. 120 male Sprague-Dawley rats were randomly divided into 7 groups (15 rats in each group, 30 rats in model group). Rats in the model control group, positive medicine group, and high, moderate and low Fu-Fang-Bie-Jia-Ruan-Gan-Pian groups were injected with 1mg.Kg-1 LPS two times at the interval of 14 days by trachea, and rats in sham-model control group with same volume normal saline. 28 day after the first injection, oral administration of drug daily until they were killed 1 day before. Fu-Fang-Bie-Jia-Ruan-Gan-Pian solution of different dosages (1.4g/Kg.d,0.7g/Kg.d,0.35g/Kg.d) was respectively given to rats in the high, moderate and low Fu-Fang-Bie-Jia-Ruan-Gan-Pian group by gavage, while equal volume of normal saline was given to those in the sham-model control group and model control group, and an equal volume of prednisone(0.56mg·kg-1·d-1) was saline was given to those in positive medicine control group.After the 8w treatment, animals were sacrificed and the TNF-α,IL-8,IL-6 contents in serum and in BALF were analysed, as well as the SOD, GSH,MDA, HYP in lung tissue. The levels ofⅣ-collagen, laminin and fibronectin in serum were determined. The part lung samples were formalin-fixed, embedded in paraffin and stained with hematoxylin and eosin. Mallory stain were used for evaluate collagen. The other part samples were homogenated to analyse the protein of TGF-β1.2. For the further elucidating the mechanism of airway remodeling intervened by Fu-Fang-Bie-Jia-Ruan-Gan-Pian, cell model of human bronchi epithelium stimulated by LPS were used as to analyse the MMP-9mRNA and TIMP-1mRNA expression intervened by Fu-Fang-Bie-Jia-Ruan-Gan-Fang drug serum. |
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