血红素氧合酶-1对哮喘小鼠模型IL-25和MUC5AC表达的影响

摘要：目的　探讨血红素氧合酶-1（HO-1）对哮喘小鼠气道炎症的调节作用及其机制。方法　将28只健康雌性Balb/c小鼠根据随机数字表法分为4组：对照组、哮喘组、血晶素组、福多司坦组，每组7只。哮喘组、血晶素组和福多司坦组小鼠于第1天和第14天腹腔注射20 μg卵清蛋白（OVA）+500 μg Al（OH）3+0.2 mL PBS致敏，于第25~28天每天雾化吸入1次OVA激发气道高反应制备小鼠哮喘模型，对照组以等量生理盐水替代，血晶素组致敏前1、2 d，致敏后12、13、23、24、27 d腹腔注射血晶素75 μmol/kg，福多司坦组分别于致敏前25、26、27 d灌胃给药福多司坦（200 mg/kg），末次激发后24 h内处死小鼠并收集血液、肺组织。HE染色观察肺组织形态学改变，免疫组化检测肺组织黏蛋白5AC（MUC5AC）的表达，酶联免疫吸附测定（ELISA）法检测肺组织中MUC5AC和血清中白细胞介素（IL）-25的水平，并对MUC5AC和IL-25进行相关性分析。结果　哮喘组肺组织可见大量炎症细胞浸润、气管黏膜增厚、黏膜下水肿，血晶素组和福多司坦组可见少量炎症细胞浸润及渗出，病理改变较哮喘组轻。与对照组相比，哮喘组、血晶素组、福多司坦组MUC5AC和IL-25的表达水平明显升高（P＜0.05）；与哮喘组相比，血晶素组和福多司坦组MUC5AC和IL-25降低（P＜0.05），且血晶素组较福多司坦组降低更明显（P＜0.05）。MUC5AC与IL-25的表达水平呈正相关（r=0.932，P＜0.01）。结论　HO-1可下调哮喘小鼠MUC5AC和IL-25的表达，减轻气道炎症和黏液高分泌。

Effects of heme oxygenase -1 on MUC5AC and IL-25 in asthmatic mice

Abstract: Objective　To explore the regulatory effect and mechanism of heme oxygenase-1 on airway inflammation in asthmatic mice. Methods　Twenty-eight healthy BALB/C female mice were randomly divided into four groups: asthma group, fludostame group, hemin group and control group. Asthma group, fludostame group and hemin group were sensitized by intraperitoneal injection of 20 μg ova + 500 μg Al (OH) 3 + 0.2 mL PBS at the day 1, 14, and ovalbumin was also given by aerosol inhalation, once a day from the day 25 to 28 to build the model of asthma mice by stimulating airway hyper responsiveness. The control group was replaced by the same amount of normal saline, and hemin group was injected intraperitoneally 75 μmol/kg of hemin at the day 1, 2 before sensitization, the 12, 13, 23, 24 and 27 after sensitization. Fludostame group was given fludostame (200 mg/kg) by gavage at the day 25, 26 and 27 before sensitization. 24 hours after sensitization. Samples of blood and lung tissue were collected. The morphological changes of lung tissues were observed by HE staining. The expression of MUC5AC in lung tissue was detected by immunohistochemistry. The levels of MUC5AC in lung tissue and IL-25 in serum were detected by enzyme-linked immunosorbent assay (ELISA). The correlation between MUC5AC and IL-25 was analyzed. Results　A large number of inflammatory cell infiltration, tracheal mucosal thickening and submucosal edema were observed in the lung tissue of asthmatic mice. A small amount of inflammatory cell infiltration and exudation were observed in hemin group and fudosteine group, and the pathological changes were less severe than those in asthma group. Compared with control group, the expression levels of MUC5AC and IL-25 were significantly increased in asthma group, hemin group and fudosten group (P＜0.05). Compared with asthma group, MUC5AC and IL-25 expression levels were significantly decreased in hemin group and fudosteine group (P＜0.05), and the reduction was more significant in the hemin group than in the fudosteine group. The expression levels of MUC5AC and IL-25 were positively correlated (r=0.932, P＜0.01). Conclusion　HO-1 can down regulate the expression levels of MUC5AC and IL-25 in asthmatic mice, reduce airway inflammation and mucus hypersecretion.