白三烯受体拮抗剂抑制哮喘大鼠气道重塑的研究

摘要

目的 应用白三烯受体1拮抗剂孟鲁斯特( montelukast,MK)治疗大鼠急性哮喘,探讨MK对核转录因子KB(NF-KB)及基质金属蛋白酶9(matrix metalloproteinase-9,MMP-9)水平的影响.方法 卵白蛋白(OVA)致敏并激发Wistar大鼠建立急性哮喘模型.给予MK 5 mg/kg或生理盐水灌胃7天.于末次OVA吸入后24小时内取材.苏木精-伊红、刚果红染色观察肺组织炎症细胞的渗出；免疫组化法:检测各组大鼠肺组织NF-KB、MMP-9的表达.结果 哮喘模型组NF-KB(0.34±0.03)OD vs MK治疗组(0.26±0.03)OD vs对照组(0.16±0.03) OD,哮喘模型组MMP-9(0.28±0.02)OD vs MK治疗组(0.23±0.02)OD vs对照组(0.17±0.01) OD.哮喘模型组较MK治疗组明显升高,MK治疗组较正常对照组升高,3组比较差异有统计学意义(P＜0.01).直线相关分析示NF-KB和MMP-9呈正相关关系(r =0.835,P＜0.01).结论 白三烯受体拮抗剂可通过抑制NF-KB、MMP-9的活性,抑制哮喘的气道重塑.%Objective To explore the effects of montelukast(MK),a selective cysteinyl leukotriene receptor 1 antagonist on nuclear factor-kB(NF-kB) and matrix metalloproteinase-9, MMP-9) production during MK treatment of mouse acute asthma. Methods Sensitized Wistar mice were challenged by ovabumin (OVA) to establish acute asthmatic model. MK(MK group) (5 mg/kg)or saline(saline group) were given by stomach for seven days. Samples were collected at 24 hours after the last OVA challenge. Cellular infiltration in lung tissue was observed with HE and Congo red stain. Expression of NF-RB and MMP-9 were observed by immunocytochemistry. Results NF-kB in asthmatic model group (0. 34±0. 03) OD vs MK treated group (0. 26±0. 03) OD vs control group (0. 16±0. 03) OD( MMP-9 in asthmatic model group(0. 280± 02) vs MK treated group(0. 23±0.02) OD vs control group (0.17±0.01) OD,NF-kB and MMP-9 level in asthmatic model group were significantly higher than those in MK treated group and control group ( P <0. 01). NF-KB and MMP-9 levels in MK treated group were higher than those of control group( P <0. 01). The expression of NF-KB in trachea was positively correlated with the expression of MMP-9 in trachea in asthmatic mouse( r=0.835. P <0. 01). Conclusion Cysteinyl leukotriene receptor 1: antagonist MK exerts its anti-airway remodeling mainly through the depression of NF-KB and MMP-9. It is concluded that MK is an effective medication for asthma.