寒喘舒对支气管哮喘模型小鼠气道重建的影响

Effect of Hanchuanshu(HCS) on airway remodeling in bronchial asthma model mice

目的观察寒喘舒对卵蛋白诱导的哮喘模型气道重建的影响。方法 BA LB/c小鼠随机分为空白对照组(A组)、哮喘模型组(B组)、寒喘舒低剂量组(C组)、寒喘舒高剂量组(D组),每组12只。采用OVA腹腔注射和雾化吸入致敏,建立支气管哮喘小鼠模型,于雾化激发哮喘后4周开始用药,1次/d,共用药8周。检测相关气道重建指标的变化。结果成功建立哮喘模型并在此基础上有气道重建表现,应用寒喘舒后,pH、PaO_2,PaCO_2均有所改善,其中高剂量的PaO_2上升,PaCO_2下降与模型组比较有显著差异(P<0.05)。模型组(B组)BALF中MIP-1A、VEGF含量均明显高于空白对照组(A组)(P<0.05),Ig E含量均明显高于空白对照组(A组)(P<0.001),寒喘舒低剂量组(C组)和高剂量组(D组)与B组比较差异具有显著性,且具有显著性(P<0.05),IgE含量均明显低于模型对照组(B组)(P<0.001)。模型组小鼠支气管发生明显改变,出现气道纤毛倒伏粘连,上皮细胞变性坏死,糜烂脱落,气道管壁粘膜充血水肿,气道上皮杯状细胞大量增生,管腔狭窄,腔内粘液增多,管壁见大量淋巴细胞浸润,肺泡腔间隔扩大,增厚,说明模型制作成功。治疗组与模型组比较,肺内细支气管周围炎性细胞有所减少,肺泡腔间隔扩大,增厚程度减轻,上皮杯状细胞增生程度降低,高剂量组气道壁结构完整,炎性细胞浸润减少,免疫组化结果显示,模型组与正常组比较,肺组织中ADAM33蛋白表达水平呈现显著升高,模型组强染色,呈棕色染色,而寒喘舒组ADAM33的表达水平低于模型组,为淡的黄色表现,可见ADAM33表达较弱。结论利用卵蛋白诱发小鼠的模型,在此基础上应用寒喘舒治疗后,高低剂量均有效,但高剂量效果更好。

Objective To observe the effects of Hanchuanshu(HCS) on airway remodeling in asthma model induced by ovalbumin. Method BA LB/c mice were randomly divided into four groups,control group(group A),asthma model group(group B),HCS high dose and low dose group(group C and group D). The OVA intraperitoneal and nebulized inhalation sensitization was used to establish a bronchial asthma mouse model. After nebulization of asthma,mice started to receive treatments with group accordance from the 4 th week,once a day until the 8 th weekends. The end of the experiment,changes was detected in relevant indicators of airway reconstruction. Result The successfully established asthma model and airway reconstruction based on model mice performance. With the aid of HCS administration,the blood p H and levels of PaO_2,PaCO_2 in mice of group c and d were improved. PaO_2 of High doses group mice were rise,while PaCO_2 decreased,compared with the model group were significantly different(P<0.05).The levels of MIP-1 A and VEGF in BALF of model group(group B) were significantly higher than those of control group(group A)(P<0.05). Ig E levels of group c and d were significantly higher than control group(A group)(P<0.001);compared with group B,the difference was remarkable(P<0.05),but Ig E levels were nonnegligible lower than the model group(B group)(P<0.001). The bronchial changes of the model group mice were obvious,which appeared in the airway ciliated lodging adhesion,epithelial cell degeneration and necrosis,erosion and exfoliation,airway wall mucosal hyperemia and edema,airway epithelium goblet cells hyperplasia,stenosis,lumen mucus Increased,observed large number of lymphocytic infiltration,alveolar space expanded,thickening,indicating successful model. Compared with the model group,in group c and d,all of the number of inflammatory cells around the bronchioles,the alveolar septa,the degree of thickening,and the degree of epithelial goblet cell proliferation decreased. The structure of the airway wall in high dose group was intact while inflammatory cell infiltrated. The results of immunohistochemistry showed that the expression of ADAM33 protein in lung tissue of model group was significantly higher than that of normal group b. As the model group was strongly stained and brown stained and group c and d expression were weak,light yellow performance level of ADAM33 was observed to be lower than model group. Conclusion The model of mice induced by ovalbumin was used for HCS study. Results showed both high and low doses of HCS were effective,but the effect of high dose was better.