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Dexamethasone Modulates Expression of Matrix Metalloproteinase in Asthmatic Rats: A Role in Airway Remodeling FREE TO VIEW

Yi Ming Yuan, MD; Zeng Li Wang, MD; Bi Rong Dong, MD
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West China Hospital of Sichuan University, Chengdu, China


Chest. 2003;124(4_MeetingAbstracts):87S. doi:10.1378/chest.124.4_MeetingAbstracts.87S-a
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PURPOSE:  To observe the effect of dexamethasone on airway remodeling and to explore significance of the balance between matrix metalloproteinase and 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 following parameters that reflects thickness of airway wall were measured by image analysis system: bronchial basement membrane perimeter (Pbm), total bronchial wall area (WAt), inner wall area (WAi) and smooth muscle area (WAm). Expression levels of MMP-2 and TIMP-1 mRNA in the lungs were assessed by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR).

RESULTS:  (1) WAt/Pbm,WAi/Pbm and WAm/Pbm in asthmatic group [(25.3±2.1)μm2/μm, (20.4±2.3)μm2/μm, (4.2±2.0)μm2/μm, respectively] were significantly higher than that in control group [(20.8±1.3)μm2/μm,(15.3±2.1)μm2/μm, (3.1±1.1)μm2/μm](p<0.01). The differences between control and dexamethasone group [(21.3±2.4)μm2/μm, (14.2±2.5)μm2/μm, (3.2±1.0)μm2/μm] 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 that 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) In control and dexamethasone group (r=0.67,0.58.p<0.05) but not in asthmatic group (r=0.24, p>0.05), there was a significantly positive correlation between MMP-2 and TIMP-1 mRNA.

CONCLUSION:  Dexamethasone could prevent airway remodeling by downregulating expression of MMP and TIMP and restoring the balance between MMP and TIMP.

CLINICAL IMPLICATIONS:  Selective MMP inhibitors may provide a novel strategy for treatment of asthma.

DISCLOSURE:  Y. Yuan, None.

Monday, October 27, 2003

2:30 PM - 4:00 PM




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