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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 LY294002, an inhibitor of phosphoinositide-3 kinase (PI3K), on airway inflammation and macrophage migration inhibitory factor (MIF) expression in ovalbumin (OVA) -induced asthma in mice. Methods Thirty Balb / c mice were randomly divided into three groups: LY294002 group, OVA group and normal control group. Through multiple intraperitoneal injections of OVA sensitization and repeated aerosol excitation, a mouse model of asthma was established. Bronchoalveolar lavage fluid (BALF) and bone marrow samples were harvested 48 hours after the final antigen challenge, and the total number of cells and eosinophils (EOS) were counted. Pulmonary histology was performed and bronchial epithelial cells were stained for periodic acid-Schiff reaction And the total number of negative cells. In the last antigen challenge 24 h, 48 h, 72 h of collecting mice vena cava blood 3 mL, using ELISA method to measure the level of serum MIF. Results Compared with OVA group, the total number of BALF cells and the number of EOS in LY294002-treated mice decreased significantly (Pa <0.05). Bronchioles of the lung tissue, perivascular EOS infiltration were controlled, respiratory mucus secretion decreased; antigen-induced respiratory inflammation was completely inhibited, and normal mice lung tissue sections are basically the same. Serum MIF levels of 24 h, 48 h and 72 h after OVA stimulation were significantly higher than those of normal control group [t (24 h) = 2.105, P = 0.04; t (48 h) = 2.205, P = 72 h) = 1.893, P = 0.05]. There was no significant difference in serum MIF levels between the LY294002 group and the control group at the 24 h, 48 h, 72 h after the last antigen challenge [t (24 h) = 0.336, P = ; t (48 h) = 0.291, P = 0.90; t (72 h) = 0.374, P = 0.76]. Serum MIF levels in the OVA group at 24 h, 48 h and 72 h after LPS challenge were significantly higher than those in the LY294002 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 PI3K inhibitor LY294002 can inhibit airway inflammation in OVA-sensitized asthmatic mice, and MIF may play a role in the development of airway inflammation in mice.