CAJ | 학술논문

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.
목적 연합응용중조가용성IL-13수체α2(sIL-13Rα2)급중조가용성IL-5수체(sIL-5R)치료지기관효천(간칭효천)소서모형,관찰대지기관폐포관세액(BALF)기산립세포(EOS)조망솔이급기산립세포추화인자(Eotaxin)수평적영향병탐토기상관궤제.방법 장50지BALB/c소서수궤분성5조:정상대조조、효천조、sIL-13Rα2치료조、sIL-5R치료조급연합치료조.계란백단백(OVA)건립효천소서모형.sIL-13Rα2치료조、sIL-5R치료조급연합치료조매차격발전30 min분별복강주사sIL -13Rα2100 μg、sIL-5R 100 μg급sIL-13Rα2、sIL-5R각100 μg간예,정상대조조급효천조생리염수대체.응용류식세포술(FCM)검측각조BALF중EOS조망솔,매련면역흡부시험(ELISA)측정Eotaxin수평.결과 ①여정상대조조비교,효천조BALF중EOS수목백분비、Eotaxin수평균현저승고(P치균＜0.01),EOS조망솔명현하강(P＜0.01).②여효천조비교,sIL-13Rα2치료조、sIL-5R치료조급연합치료조BALF중EOS수목백분비급Eotaxin수평균명현강저(P치균＜0.01),EOS조망솔명현증고(P＜0.05).③여단독치료조비교,연합치료조효과경가(P＜0.05).결론 연합응용sIL-13Rα2급sIL-5R능구명현증가효천소서EOS조망,명현강저Eotaxin수평,가명현감소EOS폐부침윤,개선기도염증,교단용경구유림상응용개치.
Objective 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.