P38蛋白激酶抑制剂SB203580对哮喘小鼠肥大细胞活化的影响

Effect of Specific Inhibitor of P38 Mitogen Activated Protein Kinase SB203580 on Mast Cells in a Mouse Model of Asthma

目的:探讨P38蛋白激酶抑制剂SB203580对哮喘小鼠肥大细胞活化的作用。方法:将BALB/c小鼠30只随机分为3组,即对照组、哮喘组、SB203580干预组,每组10只。哮喘组、SB203580干预组分别予以鸡卵清蛋白(OVA)致敏和激发。每次激发前1 h,SB203580干预组予以SB203580(5 mg/kg)腹腔注射,对照组与哮喘组给予等量的生理盐水腹腔注射。于末次激发24 h后收集支气管肺泡灌洗液(BALF),离心后进行细胞学分析。HE染色观察肺组织病理变化,免疫组织化学染色观察肥大细胞类胰蛋白酶(Tryptase)阳性表达。结果:与对照组相比,哮喘组小鼠BALF中炎症细胞数和肺组织Tryptase阳性表达[平均光密度(MOD)值0.239±0.011]升高(P<0.01);与哮喘组比较,SB203580干预组小鼠BALF中炎症细胞数和肺组织Tryptase阳性表达(MOD值0.195±0.005)降低(P<0.01),肺组织病理学改变减轻。结论:抑制P38蛋白激酶的活性可能对抑制哮喘小鼠肺组织肥大细胞募集和活化有一定的作用。

Objective： To explore the effects of SB203580,a special inhibitor of P38 mitogen activated protein kinase（P38 MAPK） on mast cells in a mouse model of asthma.Methods： Thirty BALB/c mice were randomly divided into three groups（n=10 each）：control group,asthmatic group and SB203580 treatment group.Mice in asthmatic group and SB203580 intervention group were sensitized and challenged by chicken ovalbumin（OVA）.One hour before challenge,mice in SB203580 intervention group were exposed to OVA aerosol,5 mg/kg SB203580 were injected intraperitoneally,while mice in control group and asthmatic group were given intraperitoneal injection of saline.All the mice were killed 24 hours after the last challenge and bronchoalveolar lavage fluid（BALF） was collected for cytological analysis.The lung slides were examined histologically.The protein expression of mast cell tryptase was measured by immunohistochemistry.Results： The number of inflammatory cells in BALF and the expression of tryptase（mean optical density,MOD： 0.239±0.011） in the lung were significantly higher in the asthmatic group than those in the control group.Compared with the asthmatic group,the number of inflammatory cells in BALF were less,the expression of tryptase（MOD： 0.195±0.005） in the lung the treatment group was lower,and the histopathologic lesions of lung tissue reduced.Conclusion： SB203580 has a certain role on the inhibition of recruitment and activation of mast cells in asthmatic mice.