不同糖皮质激素治疗对肥胖哮喘小鼠全身和气道的影响

Systemic and pulmonary effect of two glucocorticoids on obese mice with asthma

目的对比布地奈德雾化治疗和地塞米松口服治疗对肥胖哮喘小鼠的疗效和炎症改变。方法将75只C57/6J小鼠随机分为5组,正常组(A组)、哮喘组(B组)、肥胖哮喘组(C组)、布地奈德雾化治疗组(D组)、地塞米松口服治疗组(E组),建立饮食诱导的慢性肥胖哮喘模型。末次激发后24 h,取肺泡灌洗液(BALF)进行细胞计数及分类,ELLISA法测定血清中IL-17浓度,肺组织病理切片观察各组小鼠炎症评分,测定气管壁总面积(WAt)、气道平滑肌面积(WAm)和管腔基底膜周长(Pbm)。结果除A组外,其余四组小鼠均出现不同程度的哮喘发作,实验结束前B组无小鼠死亡,C组有2只小鼠死亡,D组有1只小鼠死亡,而E组有5只小鼠死亡。C组BALF中白细胞总数,中性粒细胞数、嗜酸性粒细胞数、血清IL-17浓度以及病理切片炎症评分、气管壁总厚度(WAt/Pbm)、气道平滑肌厚度(WAm/Pbm)明显高于A、B两组。两治疗组的BALF中白细胞总数、嗜酸性粒细胞数,以及病理切片炎症评分均较C组下降,但气管壁总厚度(WAt/Pbm)、气道平滑肌厚度(WAm/Pbm)改善不明显(P>0.05)。E组血清IL-17浓度较C组下降(P<0.05),但D组和C组无显著性差异(P>0.05)。结论雾化布地奈德能够改善肥胖哮喘小鼠的气道炎症,但不能改善气道重建和全身炎症。地塞米松口服治疗虽有助于改善肥胖哮喘的全身炎症反应,但气道重建无益,且带来更高的病死率。

Objective To evaluate the systemic and pulmonary effect of two glucocorticoids on obese mice with asthma. Methods The chronic obese asthma mice models were established by OVA sensitization and challenged with high fat diet in 75 female C57 /6J mice which were randomly divided into five groups： the normal group（ the group A）,the asthma group（ the group B）,the obese asthma group（ the group C）,the budesonide group（ the group D）,and the dexamethasone group（ the group E）. Bronchoalveolar lavage fluid（ BALF） was collected for leukocytes count and analysis. Serum IL-17 was detected by ELLISA. The airway inflammation and remodeling indexes,including inflammation score,total bronchial wall area（ WAt）,smooth muscle area（ WAm）,and bronchial basement membrane perimeter（ Pbm）,were measured in the airway pathological slices with HE staining,PAS staining and Masson staining. Results Asthma attack was developed after challenges in the groups B - E. There were 2 mice in the group C,1 mouse in the group D and 5 mice in the group E died before operation. The leukocyte numbers of BALF and the inflammation score of pathological slices decreased after glucocorticoid treatment in the group D and the group E. Serum IL-17 reduced in the group E significantly. WAt / Pbm and WAm / Pbm in the group C were higher than in the group B,but there was no significant difference among the group C,the group D and the group E. Conclusion Nebulized budesonide can reduce the airway inflammation in obese asthma,but has no benefit for systemic inflammation and airway remodeling. Oral dexamethasone can decrease serum IL-17 concentration,but have no benefit for airway remodeling and mortal rate.