CAJ | 학술논문

目的通过观察IL-5可溶性受体(sIL-5Rα)及IL-4突变体(IL-4 mutant,IL-4MT)对哮喘小鼠气道高反应性(airway hyperresponsiveness,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-5Rα治疗组和IL-4MT联合sIL-5Rα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30 min,IL-4MT治疗组、sIL-5Rα治疗组及联合治疗组分别腹腔注射IL-4MT 100 μg、sIL-5Rα 100 μg、IL-4MT和sIL-5Rα各100μg,正常对照组与哮喘组用生理盐水替代.末次激发24 h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BALF IgE、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＜0.05),联合治疗组下降更明显;与sIL-5Rα治疗组相比,联合治疗组肺阻力显著降低(P＜0.05).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＜0.01);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＜0.01);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(P＜0.05).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-5Rα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.
목적 통과관찰IL-5가용성수체(sIL-5Rα)급IL-4돌변체(IL-4 mutant,IL-4MT)대효천소서기도고반응성(airway hyperresponsiveness,AHR)급IgE、γ간우소(IFN-γ)수평적영향,탐토기잠재적림상응용개치.방법 수궤장50지BALB/c자성소서분성5조,분별위정상대조조、효천조、IL-4MT치료조、sIL-5Rα치료조화IL-4MT연합sIL-5Rα치료조(간칭연합치료조).채용복강주사란단백(ovalbumin,OVA)여경양화려혼현액대소서진행치민,란단백무화,건립소서효천모형,기중정상대조조용생리염수체대.무화전30 min,IL-4MT치료조、sIL-5Rα치료조급연합치료조분별복강주사IL-4MT 100 μg、sIL-5Rα 100 μg、IL-4MT화sIL-5Rα각100μg,정상대조조여효천조용생리염수체대.말차격발24 h후,용불동농도적록화을선담감격발각조소서,측정기폐조력,ELISA법관찰비교각조혈청급BALF IgE、IFN-γ수평변화,폐조직행HE염색,관찰병리변화.결과 여정상대조조상비,효천조폐조력현저증가(P＜0.01);여효천조상비,IL-4MT조화연합치료조폐조력현저강저(P＜0.05),연합치료조하강경명현;여sIL-5Rα치료조상비,연합치료조폐조력현저강저(P＜0.05).여정상대조조상비,효천조혈청급BALF중IgE함량현저승고,IFN-γ함량현저하강(P＜0.01);여효천조상비,연합치료조혈청급BALF중IgE함량현저하강,IFN-γ함량현저승고(P＜0.01);여단독치료조상비,연합치료조혈청급BALF중IgE함량현저하강,IFN-γ함량현저승고(P＜0.05).여효천조비,단독치료조여연합치료조폐조직염증세포삼출、침윤급대기도상피적염성손상명현감경,연합치료조감경경명현.결론 연합응용sIL-5Rα여IL-4MT가이명현감경효천소서AHR,강저혈청급BALF중IgE함량,동시승고IFN-γ함량,감경기도염증.
Objective By observing the effect of IL-5 soluble receptor α (sIL-5Rα) 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-5Rα treatment group and IL-4MT+sIL-5Rα 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,sIL-5Rα treatment group and combined treatment group were injected with IL-4MT (100 μg),sIL-5Rα(100 μg),IL-4MT (100 μg) and sIL-5Rα (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 sIL-5Rα 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 and BALF of the combined treatment group decreased significantly,the content of IFN-γ was significantly increased (P ＜0.01).Compared with the single treatment group,the content of IgE in serum and BALF of the combined treatment group decreased significantly,and the content of IFN-γ was significantly increased (P ＜0.05).Compared with the asthma group,the inflammatory cell infiltration and invasion in lung tissue and airway epithelial inflammatory injury of the single treatment group and the combined treatment group was milder significantly,and the combined treatment group was more obviously.Conclusions Combined application of sIL-5Rα and IL-4MT can significantly reduce the AHR of asthmatic mice,decrease the content of IgE in serum and BALF,increase the content of IFN-γ,reduce airway inflammation.