哮喘大鼠模型血清IL-12及IL-18的变化及相关性研究

Changes of serum IL-12 and IL-18 levels in asthmatic rat models and their correlation

目的:探讨哮喘大鼠模型血清中白细胞介素-12(IL-l2)与白细胞介素-18(IL-l8)之间的关系及其在气道炎症发生中的机制.方法:48只Wistar大鼠随机分为3组,分别为正常对照组、哮喘组、地塞米松干预组,用卵白蛋白(OVA)腹腔注射致敏,雾化吸入OVA激发制备大鼠哮喘模型,对照组用生理盐水代替OVA,地塞米松干预组每次雾化前经腹腔注射地塞米松.雾化激发后24h取各组肺泡灌洗液进行嗜酸性细胞计数,并用ELISA方法测定血清IL-l2,IL-l8的水平,分析二者相关性.结果:哮喘组、地塞米松组和对照组血清IL-12水平分别为(53.1±9.6)ng/L,(82.4±8.1)ng/L和(140.1±13.4)ng/L,与哮喘组比较,地塞米松组血清IL-12水平显著升高,但低于对照组(P<0.01).三组血清IL-18水平分别为(353.5±11.9)ng/L,(250.6±8.4)ng/L和(100.5±12.7)ng/L,哮喘组与地塞米松组显著高于对照组(P<0.01).肺泡灌洗液中嗜酸性细胞数(49.3±4.0)×105/L,(31.9±3.6)×105/L和(14.8±4.1)×105/L,哮喘组与地塞米松组显著高于对照组.哮喘组血清IL-l2,IL-l8水平分别与肺泡灌洗液中EOS数量进行两两相关分析,显示IL-12与肺泡灌洗液EOS呈负相关(r=-0.746,P<0.01),而IL-18与肺泡灌洗液EOS呈正相关(r=0.682,P<0.01).结论:IL-l2与IL-l8可能共同参与哮喘气道炎症发病过程,并且两者的作用相互拮抗.

AIM： To investigate the levels of serum interleukin- 12（IL-L2） and interleukin-18 （IL-18） in asthmatic rat, so as to analyze the relation between the two cytokines and airway inflammation. METHODS： Forty-eight Wistar rats were randomly divided into 3 groups： asthma group, dexamethasone group, and normal control group. Rats in asthma and dexamethasone groups were sensitized by intraperitoneal injections of ovalbumin （OVA） and Al（OH）3 on day 0 and 7. From day 8, rats were challenged with 1% OVA aerosol for 30 min, contineously for 7 d. Rats in dexamethasone group were intraperitoneally injected dexamethasone before each challenge. Rats in normal group were only sensitized and challenged with saline instead. Twenty-four hours after last challenge, the measurement of serum IL-12 and IL-18 levels with enzyme linked immunosorbent assay and the count of eosinophils in bronchoalveolar lavage fluid BALF were performed. RESULTS： Serum IL-12 levels in asthma group, dexamethasone group, and normal control group were （53. 1 ± 9.6） ng/L, （82.4 ±8. 1） ng/L and （140. 1 ± 13.4） ng/L, respectively. Compared with asthma group, IL-12 level in dexamethasone group increased significantly, but it was lower than normal group（P 〈0.01 ）. IL-18 levels in these 3 groups were （353.5 ± 11.9）ng/L, （250.6 ±8.4）ng/L and （100.5 ±12.7） ng/L, respectively; they were higher in asthma and dexamethasone groups than in normal group （ P 〈 0.01 ）. Eosinophils from BALF in the 3 groups were （49.3 ±4.0） × 10^5/L, （31.9 ±3.6） × 10^5/L and （ 14.8 ±4.1 ） × 10^5/L, respectively; they were significantly more in asthma and dexamethasone groups than in norreal group（ P 〈 0.01 ）. Correlation analysis of IL-12, IL-18 levels with eosinophil count in BALF of asthma group rats revealed that there was a negative correlation between IL-12 and eosinophil （r = -0. 746, P 〈0.01 ）, while there was a positive correlation between IL-18 and eosinophil （r = 0. 682, P 〈 0. 01 ）. CONCLUSION： IL-12 and IL-18 might play roles in the pathogenesis of asthma, and their effects are antagonistic.