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《The Journal of Clinical Pediatrics》 2006-08
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Effect of leukotrienes receptor antagonist on the expressional levels of matrix metalloproteinase- 9 and its inhibitor TIMP- 1 in rats with asthma

QIAO Hong- mei,LU Ji- rong,CHENG Huan- ji,LIU Li,MA Qing- shan,FU Wen- yong,ZHAO Fang- xing1 . Department of Pediatrics,The First Hospital of Jilin University,Jilin Changchun 130021,China (1.Children's Hospital of Changchun,Jilin Changchun 130061,China)  
Objective To investigate the role of matrix metalloproteinase- 9 (MMP- 9) and its inhibitor,tissue inhibitor of metalloproteinase (TIMP- 1) in the pathogenesis of bronchial asthma,and assess the effect of leukotrienes receptor antagonist on the expressional levels of MMP- 9 and TIMP- 1 in rats with asthma. Methods Forty male SD rats with the weight of 160 ~ 200 grams were divided into four groups,consisting of control group (A group) with the inhalation of PBS substituted for antigen fluid;7 d asthma group (B group) with the inhalation of antigen fluid for 7 days, 21 d asthma group (C group)with the inhalation of antigen fluid for 21 days, and treat group (D group) with the administration of leukotrienes receptor antagonist "Montelukast" at the dose of 1 mg/(kg·d) for two weeks intragastrically after the inhalation of the antigen fluid for 7 days, respectively. The expressions of genes and their products of MMP- 9 and TIMP- 1 in lung tissue were detected using immunocytochemistry, RT- PCR and Western blotting in all rats of four groups. Results There was a significant difference in the expression levels of MMP- 9 mRNA and TIMP- 1 mRNA among A group(0.64 ± 0.13 and 0.71 ± 0.10),B group (2.74 ± 0.41 and 1.53 ± 0.21), C group (1.69 ± 0.25 and 1.98 ± 0.28),and D group (0.91 ± 0.20 and 1.03 ± 0.17),respectively (F = 123.42,P 0.01;F = 65.59,P 0.01). The synthetic levels of MMP- 9 and TIMP- 1 proteins using Western blotting were correspondent with the expressional levels of their genes with the decreased synthetic level of MMP- 9 and TIMP- 1 obviously in D group in comparison with those in both of asthma groups. Conclusions There are a significant increase in the gene expressions and the protein syntheses of MMP- 9 and TIMP- 1 in rats with asthma comparing to that in normal controls. The leukotrienes receptor antagonist can down- regulate the expressions of MMP- 9 and TIMP- 1 which may be one of the mechanisms for the inhibition of airway inflammation and remold of airway in patients with asthma probably.
【CateGory Index】: R562.25
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