奥马珠单抗对过敏性哮喘小鼠气道重塑的影响

Effects of Omalizumab on airway remodeling in allergic asthma mouse

目的研究奥马珠单抗对卵清蛋白诱导的过敏性哮喘小鼠模型气道重塑的影响,评估奥马珠单抗在哮喘气道重塑方面的疗效。方法采用野生型BALB/c雌性小鼠(6~8周龄),建立周期为44 d的卵清蛋白诱导的慢性哮喘小鼠模型。设立4组:正常组、模型组、治疗组和模型对照组。检测各组小鼠肺泡灌洗液细胞总计数及分类计数、肺组织病理学改变、肺匀浆细胞因子表达情况。结果治疗组小鼠与模型组相比,肺泡灌洗液细胞总数减少[(21.59±7.73)×10^(4)/mL比(109.83±16.54)×10^(4)/mL,P=0.011];其中,嗜酸性粒细胞计数显著降低[(9.27±5.41)×10^(4)/mL比(85.87±10.61)×10^(4)/mL,P=0.009)]。肺组织炎症细胞浸润明显减少,气道炎症减轻,苏木精-伊红染色(H&E)评分下降[(1.87±0.31)比(4.15±0.26),P<0.001];气道内黏液分泌、肺内胶原沉积均明显减轻,过碘酸-希夫(PAS)评分[(0.90±0.31)分比(2.10±0.32)分,P<0.001]和胶原阳性百分比[0.12%±0.03%比0.19%±0.05%,P=0.029]均降低。免疫组织化学染色显示治疗组小鼠气道平滑肌厚度[(4.79±0.30)μm比(6.31±0.44)μm,P<0.001]及肺组织CD31+血管计数[(7.99±9.96)/mm^(2)比(15.53±18.13)/mm^(2),P<0.001]与模型组相比减少。结论奥马珠单抗可以改善慢性过敏性哮喘小鼠的气道重塑。

Objective We aimed to study the effects of omalizumab on the airway remodeling in an allergic asthmatic mouse model induced by ovalbumin(OVA)to evaluate the function of omalizumab in the treatment of airway remodeling in asthma.Methods Using wild-type female BALB/c mice(6-8 weeks old),with a 44-days circle,the chronic asthmatic mice were induced and challenged by OVA.Mice were randomly distributed into four groups including a normal group,a model group,a treatment group and a model control group,in which inflammatory cell classification in bronchoalveolar lavage fluid,histopathological changes of the lung and expression of lung cytokine were examined.Results Compared with the model group,the mean number of total cells in bronchoalveolar lavage fluid[treatment group:(21.59±7.73)×10^(4)/mL vs model group:(109.83±16.54)×10^(4)/mL,P=0.011],predominantly eosinophils in bronchoalveolar lavage fluid[treatment group:(9.27±5.41)×10^(4)/mL vs model group:(85.87±10.61)×10^(4)/mL,P=0.009]were reduced in treatment group.The inflammatory cells infiltrating into the lung tissues and the mean lung inflammation score had obvious reduction in treatment group[treatment group:(1.87±0.31)vs model group:(4.15±0.26),P<0.001].The mean PAS score which showed mucus secretion[treatment group:(0.90±0.31)vs model group:(2.10±0.32),P<0.001]and collagen deposition[treatment group:(0.12±0.03)%vs model group:(0.19±0.05)%,P=0.029]were also reduced after omalizumab injection.Analysis ofα-smooth muscle actin(α-SMA)and CD31 immunoreactivity showed that the mice with injection of omalizumab induced a significant reduction in the thickening of the airway smooth muscle[treatment group:(4.79±0.30)μm vs model group:(6.31±0.44)μm,P<0.001]and numbers of CD31+vascular airway remodeling endothelial cells[treatment group:(7.99±9.96)/mm^(2)vs model group:(15.53±18.13)/mm^(2),P<0.001].Conclusion Omalizumab can inhibit airway remodeling in chronic allergic asthmatic mice model.