联合IL-4突变体及IL-5可溶性受体α对支气管哮喘小鼠气道炎症的影响  

Effects of IL-4 mutant combined with soluble IL-5 receptor α on airway inflammation of asthmatic mice

作　　者：张方琪[1] 唐元元[1] 王娟[1] 谭国超 李志奎[1] 

机构地区：[1]第四军医大学西京医院呼吸与危重症医学科,西安710032

出　　处：《国际呼吸杂志》2014年第7期481-485,共5页International Journal of Respiration

基　　金：基金项目：国家自然科学基金资助项目（81070028）

摘　　要：目的观察联合应用IL4突变体（IL-4MT）及IL-5可溶性受体d（sIL-5Rα）对支气管哮喘（简称哮喘）小鼠气道炎症水平的干预。方法50只雌性BALB／c小鼠随机分为正常对照组、哮喘组、IL-4MT治疗组、sIL-5Rα治疗组、联合IL-4MT及sIL-5Rd治疗组（简称联合治疗组）。哮喘组和治疗组分别给予卵蛋白（OVA）致敏和激发。其中，IL-4MT治疗组、sIL-5Rα治疗组、联合治疗组分别于激发前30min腹腔注射IL-4MT100μg、sIL-5Rα100μg及IL-4MT、sIL-5Rα各100μg进行干预，正常对照组和哮喘组给予生理盐水代替。末次激发后收集BALF计数白细胞和嗜酸粒细胞（EOS）比例；HE染色观察肺组织病理变化；ELISA法测定各组BALF中IL4、IL5、嗜酸粒细胞趋化因子（Eotaxin）水平变化；末端脱氧核苷酸转移酶介导的d-UTP切口末端标记（TUNEL）法检测肺组织EOS凋亡情况。结果与正常对照组比较，哮喘组小鼠肺组织出现典型病理损害，EOS比例（t=-50．48，P〈0．001）、IL-4（t=-12．98，P〈0．001）、IL-5（t=-20．51，P〈0．001）、Eotaxin（t=-17．56，P〈0．001）水平均显著升高，EOS凋亡率（t=5．35，P〈0．001）显著下降；与哮喘组比较，各治疗组小鼠肺组织病理损害明显减轻，EOS比例（II，4MT治疗组t=27．4，P〈0．001；sIL-5Rα治疗组t=29．41，P〈0．001；联合治疗组t=37．25，P〈0．001）明显下降；Eotaxin（IL-4MT治疗组t=6．92，P〈0．001；sIL-5Rα治疗组t-4．96，P〈0．001；联合治疗组t=9．95，P〈0．001）水平明显下降；EOS凋亡率（IL-4MT治疗组t=-4．26，P〈0．001；sIL-5Rα治疗组t=-5．81，P〈O．001；联合治疗组t=-7．28，P〈0．001）明显增高；与单独治疗组相比，联合治疗组对炎症的缓解效果更为明显。结论联合IL-4MT及sIL-5Rα可明显降低哮喘小鼠IL-5、Eotaxin水平，减少肺部EOS的浸润和增加其凋亡，可以明显缓解哮喘气道炎症。Objective To observe the effects of IL-4 mutant combined with soluble IL-5 receptor on airway inflammation of asthmatic mice. Methods Fifty female BALB/c mice were randomly divided into 5 groups： the normal control group, the asthma group, the IL-4 MT treatment group, the sIL-5Rα treatment group,the combination of IL-4 MT and sIL-5Rα treatment group. Mice in asthma group and treatment group were sensitized and challenged by OVA. Mice in treatment groups were respectively injected intraperitoneally with IL-4 MT 100 μg,sIL-5Rα 100 μg and the combination of IL-4 MT 100 /,g and sIL-5Rα 100 μg 30 rain before challenged, while mice in normal group and asthma group received equal volume of saline. White blood cells（WBC） and eosinophils（EOS） in BALF were counted. HE staining was used to observe the pathological changes in lung tissue. Then the level of IL-4, IL-5 andEotaxin in BALF were measured by ELISA. Apoptosis of eosinophils in lung tissue was detected by TUNEL method. Results Compared with the normal group, the eosinophil ratio（ t =-50.48, P 〈 0. 001） and the levels of IL-4（ t =-12. 98, P〈 G0. 001）,IL-5（ t =-20. 51, P 〈0. 001）,Eotaxin（ t =-17.5（3, P 〈0. 001） in the asthma group were remarkably higher,and the apoptosis ratio （ t =5.35, P 〈0. 001） of eosinophils obviously lower. Compared with the asthma group,treatment groups can effectively reduce the eosinophils ratio （IL-4 MT treatment group t- 27.4, P 〈0. 001 ;sIL-5Rα treatment group t = 29.41, P 〈0. 001;the combination group t = 37.25, P 〈0. 001） and the levels of Eotaxin （IL-4 MT treatment group t =6.92, P 〈0. 001; sIL-5Rα treatment group t =4.96, P 〈0. 001; the combination group t = 9.95, P 〈0. 001） ,and enhance the apoptosis ratio of eosinophils （IL-4 MT treatment group t = -4.26, P 〈0. 001; sIL-5Rα treatment group t = -5.81, P 〈0. 001; the combination group t = -7.28, P 〈 0. 001）. Compared with single treatment,the combined treatment group were more effective. Conclusions IL-4

关 键 词：哮喘 IL-4突变体 IL-5可溶性受体α 嗜酸粒细胞 凋亡 

分 类 号：R562.25[医药卫生—呼吸系统]