目的观察可溶性白细胞介素-5受体α(Soluble interleukin 5 receptorα,sIL-5Rα)与可溶性白细胞介素-13受体α2(sIL-13Rα2)联合应用对哮喘小鼠气道高反应性(Airway hyperresponsiveness,AHR)及气道炎症的影响。方法将40只BALB/c小鼠随机分为正常对照组、哮喘组、sIL-5Rα组、sIL-13Rα2组和sIL-5Rα+sIL-13Rα2组,除正常对照组外,其余各组以鸡卵清蛋白(Ovalbumin,OVA)致敏和激发,建立哮喘模型,sIL-5Rα、sIL-13Rα2和sIL-5Rα+sIL-13Rα2组每次激发前30 min分别经腹腔注射sIL-5Rα100μg、sIL-13Rα2 100μg和sIL-5Rα100μg+sIL-13Rα2 100μg,正常对照组及哮喘组则用生理盐水替代。末次激发24 h后,检测各组小鼠经不同浓度氯化乙酰胆碱激发后的肺阻力,对支气管肺泡灌洗液(Bronchoalveolar lavagefluid,BALF)进行细胞计数,HE染色观察肺组织的病理变化,ELISA法检测BALF中IL-5和IL-13水平。结果与正常对照组相比,经氯化乙酰胆碱激发后,哮喘组肺阻力显著增加(P〈0.01);与哮喘组相比,sIL-13Rα2和sIL-5Rα+sIL-13Rα2组肺阻力显著降低(P均〈0.01),sIL-5Rα+sIL-13Rα2组降低更明显(P〈0.01)。与正常对照组相比,哮喘组BALF中白细胞总数和嗜酸性粒细胞(Eosinophil,EOS)数均显著增加(P均〈0.01),肺组织损害明显;与哮喘组相比,3个治疗组BALF中白细胞总数和EOS数均显著降低(P均〈0.01);与sIL-5Rα和sIL-13Rα2组相比,sIL-5Rα+sIL-13Rα2组BALF中白细胞总数和EOS数进一步降低(P均〈0.01);3个治疗组炎症细胞浸润明显减轻,炎症反应轻微,其中sIL-5Rα+sIL-13Rα2组病理变化进一步减轻。与正常对照组比较,哮喘组小鼠BALF中IL-5和IL-13水平显著升高(P〈0.01);与哮喘组相比,sIL-5Rα+sIL-13Rα2组小鼠IL-5和IL-13水平均显著降低(P〈0.01)。结论 sIL-5Rα与sIL-13Rα2联合应用可明显降低哮喘小鼠AHR,减轻气道炎症。
Objective To observe the effect of soluble interleukin-5 receptor α(sIL-5Rα) combined with soluble interleukin-13 receptor α2(sIL-13Rα2) on airway hyperresponsiveness(AHR) and airway inflammation of asthmatic mice.Methods Forty BALB/c mice were randomly divided into normal control,asthmas,sIL-5Rα,sIL-13Rα2 and sIL-5Rα + sIL-13Rα2 groups.Except those in normal control group,the mice in the other four groups were sensitized and challenged with ovalbumin to establish the mouse model of asthmas.The mice in sIL-5Rα,sIL-13Rα2 and sIL-5Rα + sIL-13Rα2 groups were injected i.p.with 100 μg of sIL-5Rα,100 μg of sIL-13Rα2 and 100 μg of sIL-5Rα + 100 μg of sIL-13Rα2 respectively 30 min before each challenge,while those in normal control and asthmas groups with physiological saline.Twenty-four hours after the last challenge,the mice in various groups were challenged with acetylcholine chloride at various concentrations and determined for airway resistance,counted for cells in broncho-alveolar lavage fluid(BALF),observed for pathological change in lung tissue by HE staining and determined for IL-5 and IL-13 levels in BALF by ELISA.Results After challenge with acetylcholine chloride,the airway resistance of mice in asthmas group increased significantly as compared with that in normal control group(each P 0.01).The airway resistance was significantly lower in sIL-13Rα2 and sIL-5Rα + sIL-13Rα2 groups than in normal control group(P 0.01),while was significantly lower in sIL-5Rα + sIL-13Rα2 group than in sIL-13Rα2 group(P 0.01).Compared with those in normal control group,the total cell and eosinophil(EOS) counts in BALF of mice in asthmas group increased significantly(P 0.01),and obvious lesion was observed in lung tissue.The total leukocyte and EOS counts in BALFs of mice were significantly lower in sIL-5Rα,sIL-13Rα2 and sIL-5Rα + sIL-13Rα2 groups than in asthmas group(each P 0.01),while significantly lower in sIL-5Rα + sIL-13Rα2 group than in sIL