摘要
目的探讨基质金属蛋白酶-9(MMP-9)及其组织抑制物(TIMP-1)在支气管哮喘发病中的作用,评价白三烯受体拮抗剂对其的调节作用。方法应用ELISA、免疫组织化学、Western-blot及RT-PCR技术对白三烯受体拮抗剂治疗前后大鼠肺组织中MMP-9及TIMP-1表达进行研究。结果①大鼠肺组织MMP-9mRNA表达:哮喘7d组为(2.74±0.41),21d组为(1.69±0.25),白三烯受体拮抗剂治疗组为(0.91±0.20),正常对照组为(0.64±0.13),组间比较差异有统计学意义(F=123.42,P<0.01)。大鼠肺组织TIMP-1mRNA表达:哮喘7d组为(1.53±0.21),21d组为(1.98±0.28),白三烯受体拮抗剂治疗组(1.03±0.17),正常对照组(0.71±0.10),组间比较差异有统计学意义(F=65.59,P<0.01)。②RT-PCR结果与Westernblot结果一致。结论从蛋白质水平及分子水平显示哮喘大鼠模型肺组织MMP-9表达升高,TIMP-1表达亦增强;白三烯受体拮抗剂可能通过下调MMP-9及TIMP-1表达来抑制气道炎症和气道重塑。
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.
出处
《临床儿科杂志》
CAS
CSCD
北大核心
2006年第8期677-680,共4页
Journal of Clinical Pediatrics