[Function of MMP/TIMP on airway remodeling of bronchial asthma and treating effects of Zhichuan capsule].
OBJECTIVE
To explore the mechanism of the bronchial asthma and to study the treating effects of Zhichuan Capsule on the airway remodeling of asthmatic model rats.


METHODS
The rat model was established by being sensitized and activated with different density of ovalbumin through prolonged and repeated exposure for 8 weeks. The rats were randomly divided into model group, Zhichuan Capsule treated group, dexameson treated group, and Zhichuan Capsule and dexameson treated group. Another group of normal rats were taken as control. General histological changes were observed by hematoxylin and eosin stained sections. Being standardized by internal perimeter (Pi), the wall thickness (d), internal area (Ai), outer area (Ao) and wall area (WA) of the airway were quantified by computer-assisted image analysis system. The express of MMP-9, TIMP-1, Col I, Col III and ColV in the airway were examined by immunocytochemical methods. During the course of airway remodeling, the dynamic changes of model rats were observed at different time points (2, 4, 6 and 8 weeks after the activating). Statistical comparison was performed by ANOVA followed by Fisher LSD test.


RESULTS
(1) Histologic examination showed eosinophil infiltration within the airway walls, epithelial damage, excessive mucus in the lumen and edema in the submucosa of the airways in model rats, and that the collagen deposition increased accompanied by increasing of TIMP-1. In the model rats, MMP-9 increased at the time point of 2 weeks, but it decreased in the late stage (8 weeks after activating) of airway remodeling. And the level of TIMP-1 was far higher than MMP-9 at the time point of 8 weeks. (2) Zhichuan Capsule could down-regulate the level of TIMP-1 in the airway wall, as well as the thickness of airway wall and the collagen deposition. And there were progressing effects when it was used together with dexameson.


CONCLUSIONS
(1) The early increase of MMP-9 is a key point to start remodeling; and the increase of TIMP-1 in the late stage, which inhibits collagenase activity, may play an important role in developing airway fibrosis. Imbalance between MMP-9 and TIMP-1 is a marker of airway remodeling. (2) Zhichuan Capsule can decrease the deposition of collagen and suppress the airway remodeling by inhibiting the TIMP-1 expression.
Wu
Yin-Gen
YG
Respiratory Department, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. wuyingensh@yahoo.com.cn
Wang
Li-Xin
LX
D000704:Analysis of Variance; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D001980:Bronchi / Q000737:chemistry / Q000187:drug effects / Q000503:physiopathology; D024042:Collagen Type I / Q000032:analysis; D024061:Collagen Type III / Q000032:analysis; D024062:Collagen Type V / Q000032:analysis; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D007150:Immunohistochemistry; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000502:physiology*; D008517:Phytotherapy; D028321:Plant Preparations / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D019714:Tissue Inhibitor of Metalloproteinases / Q000032:analysis / Q000502:physiology*
D024042:Collagen Type I; D024061:Collagen Type III; D024062:Collagen Type V; D004365:Drugs, Chinese Herbal; D028321:Plant Preparations; D019714:Tissue Inhibitor of Metalloproteinases; D020780:Matrix Metalloproteinase 9