目的通过观察IL-5可溶性受体(sIL-5Ra)及IL-4突变体(IL-4mutant,IL-4MT)对哮喘小鼠气道高反应性(airwayhyperresponsiveness,AHR)及IgE、γ干扰素(IFN-γ)水平的影响,探讨其潜在的临床应用价值。方法随机将50只BALB/c雌性小鼠分成5组,分别为正常对照组、哮喘组、IL-4MT治疗组、sIL-5Ra治疗组和IL-4MT联合sIL-5Ra治疗组(简称联合治疗组)。采用腹腔注射卵蛋白(ovalbumin,OVA)与氢氧化铝混悬液对小鼠进行致敏,卵蛋白雾化,建立小鼠哮喘模型,其中正常对照组用生理盐水替代。雾化前30rain,IL-4MT治疗组、sIL-5Ra治疗组及联合治疗组分别腹腔注射IL-4MT100μg、sIL-5Ra100μg、IL-4MT和sIL~5Ra各100μg,正常对照组与哮喘组用生理盐水替代。末次激发24h后,用不同浓度的氯化乙酰胆碱激发各组小鼠,测定其肺阻力,ELISA法观察比较各组血清及BALFIgE、IFN-γ水平变化,肺组织行HE染色,观察病理变化。结果与正常对照组相比,哮喘组肺阻力显著增加(P〈0.01);与哮喘组相比,IL-4MT组和联合治疗组肺阻力显著降低(P〈O.05),联合治疗组下降更明显;与sIL-5Ra治疗组相比,联合治疗组肺阻力显著降低(P〈O.05)。与正常对照组相比,哮喘组血清及BALF中IgE含量显著升高,IFN-γ含量显著下降(P〈O.01);与哮喘组相比,联合治疗组血清及BALF中IgE含量显著下降,IFN-γ含量显著升高(P〈O.01);与单独治疗组相比,联合治疗组血清及BALF中IgE含量显著下降,IFN-γ含量显著升高(Pd0.05)。与哮喘组比,单独治疗组与联合治疗组肺组织炎症细胞渗出、浸润及对气道上皮的炎性损伤明显减轻,联合治疗组减轻更明显。结论联合应用sIL-5Ra与IL-4MT可以明显减轻哮喘小鼠AHR,降低血清及BALF中IgE含量,同时升高IFN-γ含量,减轻气道炎症。
Objective By observing the effect of IL-5 soluble receptor a (sIL-SRa) combined with IL-4 mutant (IL-4MT) on airway hyperresponsiveness (AHR) and IgE and IFN-γ in asthmatic mice, explore its potential value in clinical application. Methods Fifty female BALB/c mice were randomly divided into five groups,which were normal control group,asthma group, IL-4MT treatment group, sIL- 5Ra treatment group and IL-4MT-sIL-SRa treatment group (the combined treatment group). The mice were sensitized by intraperitoneal injection of ovalbumin (OVA) and aluminium hydroxide suspension, and atomizd with ovalbumin, to establish a murine model of asthma, the normal control group were treated with saline instead. IL-4MT treatment group, slL-5Ra treatment group and combined treatment group were injected with IL-4MT (100 μg),slL-5Ra(100 μg), IL-4MT (100 μg) and slL-5Ra (100 μg) 30 minutes before atomization, the normal control group and asthma group were injected with saline. After the last challenge,mice were stimulated with different concentrations of acetylcholine chloride, determine the pulmonary resistance,observe and compare the changes of IgE,IFN-γ in serum and bronchoalveolar lavage fluid (BALF) by ELISA,lung tissue were stained with HE, to observe the pathological changes. Results Compared with the normal control group,the pulmonary resistance of asthma group significantly increased ( P 〈0.01). Compared with the asthmatic group, the pulmonary resistance of IL-4MT group and combined treatment group decreased significantly ( P 〈 0.05), and the combined treatment group decreased more obviously. Compared with the slL-SR~ treatment group, pulmonary resistance of the combined treatment group decreased significantly ( P 〈0.05). Compared with the normal control group, the content of IgE in serum and BALF of asthmatic group was significantly increased, the content of IFN-γ decreased significantly ( P 〈0.01). Compared with the asthma group,the content of IgE in serum