摘要目的 联合应用重组可溶性IL-13受体α2(sIL-13Rα2)及重组可溶性IL-5受体(sIL-5R)治疗支气管哮喘(简称哮喘)小鼠模型,观察对支气管肺泡灌洗液(BALF)嗜酸粒细胞(EOS)凋亡率以及嗜酸粒细胞趋化因子(Eotaxin)水平的影响并探讨其相关机制.方法 将50只BALB/c小鼠随机分成5组:正常对照组、哮喘组、sIL-13Rα2治疗组、sIL-5R治疗组及联合治疗组.鸡卵白蛋白(OVA)建立哮喘小鼠模型.sIL-13Rα2治疗组、sIL-5R治疗组及联合治疗组每次激发前30 min分别腹腔注射sIL -13Rα2100 μg、sIL-5R 100 μg及sIL-13Rα2、sIL-5R各100 μg干预,正常对照组及哮喘组生理盐水代替.应用流式细胞术(FCM)检测各组BALF中EOS凋亡率,酶联免疫吸附试验(ELISA)测定Eotaxin水平.结果 ①与正常对照组比较,哮喘组BALF中EOS数目百分比、Eotaxin水平均显著升高(P值均＜0.01),EOS凋亡率明显下降(P＜0.01).②与哮喘组比较,sIL-13Rα2治疗组、sIL-5R治疗组及联合治疗组BALF中EOS数目百分比及Eotaxin水平均明显降低(P值均＜0.01),EOS凋亡率明显增高(P＜0.05).③与单独治疗组比较,联合治疗组效果更佳(P＜0.05).结论 联合应用sIL-13Rα2及sIL-5R能够明显增加哮喘小鼠EOS凋亡,明显降低Eotaxin水平,可明显减少EOS肺部浸润,改善气道炎症,较单用更具有临床应用价值.

abstractsObjective To investigate the effects of soluble interleukin-13 receptor α2 (sIL-13Rα2)combined with soluble interleukin-5 receptor (sIL-5R) on the apoptosis of Eosinophils and Eotaxin levels in bronchoalveolar lavage fluid (BALF) of asthmatic mice and explore possible mechanisms of treating asthmatic mice with them.Methods Fifty BALB/c mice were randomly divided into five groups:naive mice,saline sham treated mice,sIL-13Rα2 treated mice,sIL-5R treated mice and sIL-13Rα2 combined with sIL-5R treated mice (combination treated mice).Animals were actively sensitized by intraperitoneal injection of ovalbumin (OVA).Mice in the latter 3 groups,30 min before challenged,were respectively injected intraperitoneally with sIL-13Rα2 100 μg,sIL-5R 100 μg and sIL-13Rα2 100 μg plus sIL- 5R100 μg.Naive mice and saline sham treated mice received equal volume of saline. The apoptotic ratios were analyzed by flow cytometry (FCM). The levels of Eotaxin were detected by enzyme-linked immunosorbent assay (ELISA).Results ①In saline sham treated mice,the ratios of Eosinophils and Eotaxin levels in BALF were remarkably higher than that in naive mice (all P ＜0.01),and the apoptotic ratios (AR) obviously lower (P ＜0.01).②Compared with saline sham treated mice,the ratios of Eosinophils and Eotaxin levels significantly decreased in sIL-13Rα2 treated mice,sIL-5R treated mice and combination treated mice (all P ＜0.01),and the apoptotic ratios (AR) obviously increased ( P ＜0.05).③Compared with single treatment,combined treatment were more effective ( P ＜0.05).Conclusions These results indicate that combination sIL-13Rα2 with sIL-5R could more promote apoptosis of Eosinophils and lower the levels of Eotaxin than their sole effects,and more efficiently relieve airway inflammation.Our findings suggest that combined treatment with these molecular targets could be a useful therapeutic strategy for asthma.