促红细胞生成素对速发型哮喘小鼠模型IL-4、IL-5及IgE指标的影响

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目的探讨促红细胞生成素(EPO)对速发型哮喘小鼠模型IL-4、IL-5及IgE的变化及肺组织病理变化的相关机制影响。方法选择54只Balb/c小鼠随机分为6组,每组9只。哮喘模型组,EPO高、中、低浓度组和地塞米松组,每间隔7 d腹腔注射20μg卵清蛋白(ovalbumin,OVA)+2 mg氢氧化铝共0.2 ml致敏3次。第22天引喘小鼠,用3%OVA溶液(生理盐水配制)雾化吸入,吸入30 min/d,持续7 d。EPO低、中、高浓度组和地塞米松组分别于雾化吸入前30 min腹腔注射低浓度EPO(500 IU/kg)、中浓度EPO(1 000 IU/kg)、高浓度EPO(2 000 IU/kg)和地塞米松(1 mg/kg)。正常对照组腹腔注射和雾化吸入的时间和方法相同只是使用生理盐水替代药品。通过酶联免疫吸附实验法(ELISA)检测血清中IL-5、IL-4和IgE水平;小鼠肺组织行切片,苏木素-伊红(HE)染色,观察其病理变化。结果EPO高、中、低浓度组,哮喘模型组和地塞米松组IL-4、IL-5及IgE浓度均高于正常对照组,差异有统计学意义(P<0.05)。EPO高、中浓度组和地塞米松组IL-4、IL-5及IgE浓度均低于哮喘模型组,差异有统计学意义(P<0.05)。正常对照组中小鼠支气管的上皮无损伤,炎症反应表现不明显,且肺组织形态无异常;而哮喘模型组中小鼠存在很多的炎性细胞,其中大部分存在于支气管及其周围血管,最终致使管腔狭窄;EPO低浓度组结果显示存在的炎性细胞及管腔狭窄程度较哮喘组减轻,随EPO浓度的增加,病理损伤程度减轻;EPO高、中和低浓度组与地塞米松组比较,管腔及平滑肌厚度相似,但地塞米松组炎性细胞浸润程度明显减轻。结论 EPO可抑制哮喘小鼠IL-4、IL-5、IgE的分泌及减轻肺组织病理改变,提示EPO对哮喘小鼠模型的炎症因子的产生具有调节作用。 Objective To investigate the effects of erythropoietin (EPO) on the changes of IL-4, IL-5 and IgE and the related mechanism of lung pathological changes in the mouse model of immediate-onset asthma. Methods Fifty-four Balb / c mice were randomly divided into 6 groups with 9 mice in each group. Asthma model group, EPO high, medium and low concentration group and dexamethasone group, intraperitoneal injection of 20μg ovalbumin (OVA) +2 mg aluminum hydroxide 0.2 ml every 7 days sensitized three times. On the 22nd day, the asthmatic mice were inhaled aerosolized with 3% OVA solution (normal saline) and inhaled for 30 min / d for 7 d. EPO (500 IU / kg), EPO (1 000 IU / kg) and EPO (2 000) were injected into the low, medium and high concentration EPO group and dexamethasone group respectively 30 min before inhalation, IU / kg) and dexamethasone (1 mg / kg). The normal control group, intraperitoneal injection and atomization of the same time and method of inhalation is to use saline instead of drugs. Serum levels of IL-5, IL-4 and IgE were detected by enzyme-linked immunosorbent assay (ELISA). Mice lung tissues were stained with hematoxylin-eosin (HE) and the pathological changes were observed. Results The levels of IL-4, IL-5 and IgE in high, middle and low concentration EPO group, asthma model group and dexamethasone group were significantly higher than those in normal control group (P <0.05). The levels of IL-4, IL-5 and IgE in EPO high, middle and dexamethasone groups were lower than those in asthma model group (P <0.05). In the normal control group, the bronchial epithelium of mice was not damaged, the inflammatory response was not obvious, and the morphology of the lung tissue was normal. In the asthma model group, there were many inflammatory cells in the mice, most of which existed in the bronchus and its peripheral blood vessels, The results of EPO low concentration group showed that inflammatory cells and luminal stenosis were less severe than those in asthma group, with the increase of EPO concentration, the degree of pathological lesion was reduced. Compared with dexamethasone group , Lumen and smooth muscle thickness were similar, but the degree of inflammatory cell infiltration in dexamethasone group was significantly reduced. Conclusion EPO can inhibit the secretion of IL-4, IL-5 and IgE in asthmatic mice and reduce the pathological changes of lung tissue, suggesting that EPO can regulate the production of inflammatory cytokines in asthmatic mice.
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