磷酸酰肌醇-3激酶抑制剂对哮喘小鼠呼吸道炎症及巨噬细胞移动抑制因子表达的影响  

Effect of Phosphoinostitide 3-Kinase Inhibitor on Airway Inflammation and Macrophage Migration Inhibitory Factor in Asthmatic Mouse Models

作　　者：喻宁芬[1] 喻宁芳[2] 邓礼[1] 于力[1] 陈英[1] 肖雪[1] 张又祥[1] 李书华[3] 

机构地区：[1]广州市第一人民医院儿科,广州510180 [2]广州市第一人民医院检验科,广州510180 [3]广州医学院病理教研室,广州510180

出　　处：《实用儿科临床杂志》2011年第16期1256-1258,共3页Journal of Applied Clinical Pediatrics

基　　金：广东省科技计划项目(73092);广州市医药卫生科技资助项目(2007-YB-026)

摘　　要：目的观察磷酸酰肌醇-3激酶(PI3K)抑制剂LY294002对卵白蛋白(OVA)诱导哮喘小鼠呼吸道炎症及巨噬细胞移动抑制因子(MIF)表达的影响。方法 Balb/c小鼠30只,随机分为3组:LY294002处理组、OVA组和正常对照组。通过OVA多次腹腔注射致敏和反复雾化激发,建立哮喘小鼠模型。末次抗原激发后48 h收集其支气管肺泡灌洗液(BALF)和骨髓标本,计数其细胞总数和嗜酸性粒细胞(EOS),并行肺组织学检查,计数细支气管上皮细胞过碘酸雪夫反应阳性和阴性细胞总数。于末次抗原激发24 h、48 h、72 h采集各组小鼠下腔静脉血3 mL,采用ELISA法测定静脉血清MIF水平。结果与OVA组比较,LY294002处理组小鼠BALF细胞总数及EOS数明显减少(Pa<0.05)。肺组织细支气管、血管周围EOS浸润得到控制,呼吸道黏液分泌减少;抗原诱导的呼吸道炎症完全得到抑制,和正常小鼠肺组织切片基本一致。OVA组末次抗原激发24 h、48 h、72 h血清MIF水平较正常对照组明显升高[t(24 h)=2.105,P=0.04;t(48 h)=2.205,P=0.04;t(72 h)=1.893,P=0.05],LY294002处理组末次抗原激发24 h、48 h、72 h血清MIF水平与正常对照组比较差异无统计学意义[t(24 h)=0.336,P=0.86;t(48 h)=0.291,P=0.90;t(72 h)=0.374,P=0.76],OVA组末次抗原激发24 h、48 h、72 h血清MIF水平较LY294002处理组明显升高[t(24 h)=2.387,P=0.04,t(48 h)=2.155,P=0.04;t(72 h)=2.424,P=0.03]。结论 PI3K抑制剂LY294002对OVA致敏的哮喘小鼠呼吸道炎症具有抑制作用,MIF可能在小鼠呼吸道炎症的发展过程中起一定作用。Objective To investigate the effect of phosphoinostitide 3-kinase inhibitor（PI3K）——LY294002 on airway inflammation and expression of macrophage migration inhibitory factor（MIF） in asthmatic mouse models induced by ovalbumin（OVA）. Methods Thirty Balb/c mice were randomly divided into 3 groups：LY294002-treated group,OVA group and normal control group.Balb/c mice in LY294002-treated group and OVA group were sensitized and challenged with OVA.Cells of bronchoalveolar lavage fluid（BALF） and bone marrow were counted and classified at 48 h post last OVA sensitized.The lung tissues of mice were sectioned to hematoxylin-eosin and pe-riodic acid Schiff staining（PAS）.The total number PAS-positive and negative cells of BALF were counted.Cavity vein blood of each group was collected at 24 h,48 h,72 h respectively,and the concentration of MIF was measured by enzyme-linked immunosorbent assay. Results OVA-induced airway infiltration of inflammatory cells and eosinophils in BALF in LY294002-treated group were reduced;there was less inflammatory infiltration and eosinophils numbers around airway and blood vessels in LY294002-treated group,and OVA-induced airway inflammation had been completely suppressed as the same as in lung histological sections.The concentrations of MIF were significantly higher in OVA group than those in the normal control group [t（24 h）=2.105,P=0.04;t（48 h）=2.205,P=0.04;t（72 h）=1.893,P=0.05],however there was no significant difference between LY294002-treated group and the normal control group [t（24 h）=0.336,P=0.86;t（48 h）=0.291,P=0.90;t（72 h）=0.374,P=0.76].The concentrations of blood MIF were significantly higher in OVA group than those in LY294002 treatment group [t（24 h）=2.387,P=0.04;t（48 h）=2.155,P=0.04;t（72 h）=2.424,P=0.03]. Conclusions The potential role of PI3K may inhibit OVA-induced asthma by attenuating airway inflammation,and MIF may play a critical role in airway inflammation with a asthmatic mouse model.

关 键 词：呼吸道炎症 哮喘 磷酸酰肌醇-3激酶抑制剂 巨噬细胞移动抑制因子 小鼠 

分 类 号：R725.6[医药卫生—儿科]