[Nitric oxide modulates expression of matrix metalloproteinase in asthmatic rats].Zhonghua Jie He He Hu Xi Za Zhi. 2002 May; 25(5):276-9.ZJ
To observe the effect of nitric oxide on expression of matrix metalloproteinase and tissue inhibitor of metalloproteinase in asthmatic rats.
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).
(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).
Nitric oxide may contribute to airway inflammation and remodeling by influencing the balance between matrix metalloproteinases and tissue inhibitors of metalloproteinases.