[Nitric oxide modulates expression of matrix metalloproteinase in asthmatic rats].
OBJECTIVE
To observe the effect of nitric oxide on expression of matrix metalloproteinase and tissue inhibitor of metalloproteinase in asthmatic rats.


METHODS
Thirty healthy male Wistar rats were randomly divided into control (n = 10), asthmatic (n = 10) and L-arginine (n = 10) groups. Lung tissues were sliced and stained with HE. The following morphometric parameters were measured by image analysis system: airway wall basement membrane perimeter (Pbm), total bronchial wall area (WAt), the inner wall area (WAi) and the area of smooth muscle (WAm). Levels of nitrites/nitrates and NOS activity in the lungs were measured by commercial NO and NOS kits. Transcriptional 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 the L-arginine group were (35.1 +/- 2.6) microm(2)/microm, (25.3 +/- 2.0) microm(2)/microm, and (8.7 +/- 1.5) microm(2)/microm, respectively. WAt/Pbm, WAi/Pbm and WAm/Pbm in the asthmatic group were (25.3 +/- 2.1) microm(2)/microm, (20.4 +/- 2.3) microm(2)/microm, and (4.2 +/- 2.0) microm(2)/microm, respectively. WAt/Pbm, WAi/Pbm and WAm/Pbm in the control group were (20.8 +/- 1.3) microm(2)/microm, (15.3 +/- 2.1) microm(2)/microm, and (3.1 +/- 1.1) microm(2)/microm, respectively. The differences among three groups were statistically significant. (2) Levels of nitrites/nitrates in the L-arginine group [(11.8 +/- 1.7) nmol/mg] and the asthmatic group [(7.2 +/- 2.1) nmol/mg] were significantly higher than that in the control group [(3.1 +/- 1.2) nmol/mg]. NOS activity in the lungs was (16.5 +/- 1.3) U/mg L-arginine group, (10.8 +/- 1.4) U/mg asthmatic group, and (1.46 +/- 0.98) U/mg control group, respectively, the differences being statistically significant between groups. (3) MMP-2 and TIMP-1 mRNA levels in the L-arginine group and the asthmatic group were significantly higher than that in the control group [L-arginine group (0.82 +/- 0.11), (0.51 +/- 0.12); asthmatic group (0.68 +/- 0.14), (0.56 +/- 0.10); control group (0.14 +/- 0.03), (0.11 +/- 0.05), respectively]. The difference in the MMP-2 mRNA levels was significant between the L-arginine group and the asthmatic group (P < 0.05), but the difference in the TIMP-1 mRNA levels between the two groups was not statistically significant. (P > 0.05). (4) A significant positive correlation was found between the MMP-2 mRNA levels and nitrites/nitrates levels in L-arginine group and asthmatic group (r(s) = 0.65, 0.68, P < 0.05), but there was no significant correlation between the nitrites/nitrates levels and the TIMP-1 mRNA levels in the two groups (r(s) = 0.23, 0.18, P > 0.05).


CONCLUSIONS
Nitric oxide may contribute to airway inflammation and remodeling by influencing the balance between matrix metalloproteinases and tissue inhibitors of metalloproteinases.
Yuan
Yiming
Y
Department of Geriatrics, The Huaxi Hospital, Sichuan University, Chengdu 610041, China.
Wang
Zengli
Z
Dong
Birong
B
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001249:Asthma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005786:Gene Expression Regulation / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020782:Matrix Metalloproteinases / Q000235:genetics*; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics
D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2