羧胺三唑联合地塞米松有效缓解小鼠过敏性气道炎症

Inhibitory effects of combined carboxyamidotriazole with dexamethasone in allergic airway inflammation

目的评价羧胺三唑(CAI)联合地塞米松对小鼠过敏性气道炎症的治疗效果,为哮喘性疾病探索安全、有效的联合用药方案。方法将小鼠分为对照组、模型组、40 mg/kg CAI治疗组(CAI40)、低剂量地塞米松治疗组(DL)、高剂量地塞米松治疗组(DH)、低剂量地塞米松联合20 mg/kg CAI治疗组(DL20)、低剂量地塞米松联合40 mg/kg CAI治疗组(DL40)。建立过敏性哮喘模型,取肺泡灌洗液(BALF),ELISA法检测其中IL-4、IL-13、IFN-γ水平;计BALF中总细胞数和嗜酸性粒细胞数;ELISA法检测血清中IgE水平;取左肺切片,HE染色后观察肺组织病理水平改变。结果与对照组相比,模型组小鼠呈现出明显的气道炎症反应,包括BALF中IL-4、IL-13水平及炎性细胞数明显升高,而IFN-g水平显著降低,血清中IgE水平显著升高,肺组织病理切片的HE染色结果呈现出明显的炎症细胞聚集浸润。与模型组相比,各治疗组均有缓解炎症的效果。联合用药组小鼠的BALF中IL-4、IL-13水平及炎性细胞数均低于CAI40组和DL组,而IFN-γ水平高于三个单药治疗组。联合用药组血清中IgE水平均低于三个单药治疗组。肺组织病理结果显示,联合用药组的肺组织炎症细胞浸润、杯状细胞增生、气道平滑肌增厚等气道重塑程度均低于CAI40组和DL组,与DH组相当。结论低剂量地塞米松联合低、高剂量羧胺三唑对卵清蛋白诱导的小鼠过敏性气道炎症有良好的治疗效果,比单药治疗组表现出更强的抗炎作用。因此,适当降低地塞米松剂量,通过联合羧胺三唑来治疗过敏性气道炎症,减少地塞米松耐药性和依赖性等不良反应,或可成为治疗过敏性气道炎的一种新方法。

Objective To evaluate the inhibitory effects of combined carboxyamidotriazole（CAI） with dexamethasone（DEX） in allergic airway inflammation. Methods The allergic asthma model was established by ovalbumin（OVA） sensitization and challenge in mice, which were divided into the following groups： control group（CON）, model group（PEG）, 40 mg/kg CAI-treated group（CAI40）, low-dose DEX-treated group（DL）, high-dose DEX-treated group（DH）, the combination of 20 mg/kg CAI with low-dose DEX treated group（DL20）, the combination of 40 mg/kg CAI with low-dose DEX treated group（DL40）. The levels of IL-4, IL-13, IFN-g in bronchoalveolar lavage（BALF） and the content of IgE in serum were measured by ELISA. Cell counting was conducted to quantify the total inflammatory cells number and eosinophils number in BALF. Lung tissues were cut into slices and stained with HE for evaluation of recruitment of infiltrated inflammatory cells. Results The model group presented severe airway inflammatory responses compared with control group. All treatment strategies effectively inhibited airway inflammatory responses. Lower levels of IL-4, IL-13 or IgE were observed in DL20 group compared with CAI40 group and DL group. In DL40 group, the IgE level in serum was significantly lower than that of DH group, and the total inflammatory cells number and eosinophils number in BALF of DL40 group were significantly less than that in DH group. Both combination groups showed milder recruitment of inflammatory cells in lung tissues compared with CAI40 group and DL group. Conclusion The airway inflammatory responses are effectively inhibited in all the treatment groups. Furthermore, better effects are seen in both combination groups than in 40 mg/kg CAI-treated group and low-dose DEX-treated group. This study may provide a new way to treat allergic airway inflammation by the combination of carboxyamidotriazole with dexamethasone, with the potential of reducing adverse reactions of glucocorticoids.