[Modulation of matrix metalloproteinase by dexamethasone in airway remodeling in asthmatic rats].
OBJECTIVE
To observe the effect of dexamethasone on airway remodeling and to explore the significance of the balance between matrix metalloproteinase and the tissue inhibitor of metalloproteinase.


METHODS
Thirty male Wistar rats were randomly divided into asthmatic group (n = 10), dexamethasone group (n = 10) and control group (n = 10). Lung tissues were sliced and stained with H. E. The parameters such as bronchial basement membrane perimeter(Pbm), total bronchial wall area(WAt), inner wall area(WAi) and smooth muscle area(WAm), which reflect the thickness of airway wall, were measured by image analysis system. The expression levels of MMP-2 and TIMP-1 mRNA in the lungs were assessed by semiquantitative reverse transcription-polymerase chain reaction.


RESULTS
1. WAt/Pbm, WAi/Pbm and WAm/Pbm in asthmatic group (25.3 +/- 2.1 microns 2/micron, 20.4 +/- 2.3 microns 2/micron, 4.2 +/- 2.0 microns 2/micron, respectively) were significantly higher than those in control group (20.8 +/- 1.3 microns 2/micron, 15.3 +/- 2.1 microns 2/micron, 3.1 +/- 1.1 microns 2/micron) (P < 0.01). The differences between those in control group and those in dexamethasone group (21.3 +/- 2.4 microns 2/micron, 14.2 +/- 2.5 microns 2/micron, 3.2 +/- 1.0 microns 2/micron) were not statistically significant (P > 0.05). 2. MMP-2 and TIMP-1mRNA levels in asthmatic group (0.68 +/- 0.14, 0.56 +/- 0.10) and dexamethasone group (0.37 +/- 0.11, 0.31 +/- 0.10) were significantly higher than those in control group (0.14 +/- 0.03, 0.11 +/- 0.05). The differences between asthmatic group and dexamethasone group were also significant (P < 0.01). 3. There was a significant positive correlation between MMP-2 and TIMP-1 mRNA in control group and dexamethasone group (r = 0.67, 0.58, P < 0.05), but not in asthmatic group (r = 0.24, P > 0.05).


CONCLUSIONS
Dexamethasone could prevent airway remodeling by downregulating the expression of MMP-2 and TIMP-1 and restoring the balance between MMP-2 and TIMP-1.
Yuan
Yiming
Y
Department of Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, China.
Wang
Zengli
Z
Dong
Birong
B
D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D001980:Bronchi / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003907:Dexamethasone / Q000494:pharmacology*; D015536:Down-Regulation; D008168:Lung / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D003907:Dexamethasone; D020778:Matrix Metalloproteinase 2