醒鼻凝胶滴鼻剂对于变应性鼻炎豚鼠鼻腔、支气管肺泡灌洗液IL-4、IL-13、TGF-β和鼻黏膜及肺组织XBP1的影响

Effect of Traditional Chinese Medicine Xingbi Gelation Nasal Drops(醒鼻凝胶滴鼻剂)on Levels of IL-4,IL-13 and TGF-βin Nasal and Bronchoalveolar Lavage Fluid and Levels of XBP1 in Nasal Mucosa and Lung Tissue of Allergic Rhinitis Guinea Pigs

目的观察醒鼻凝胶滴鼻剂对变应性鼻炎豚鼠上下气道相关的鼻腔灌洗液、支气管肺泡灌洗液白介素4(IL-4)、白介素13(IL-13)、转化生长因子-β(TGF-β)的影响,鼻黏膜及肺组织X盒结合蛋白1(XBP1)的影响,及肺组织炎症情况。方法健康普通级豚鼠60只,适应性喂养1周后,以卵清白蛋白(OVA)致敏、激发建立变应性鼻炎豚鼠模型,采用简单数字和分层随机法随机分为6组,分别为正常对照组、模型组、醒鼻凝胶滴鼻剂6.88 mg/kg剂量组、醒鼻凝胶滴鼻剂13.76 mg/kg剂量组、醒鼻凝胶滴鼻剂27.52 mg/kg剂量组、雷诺考特组;10只/组。并于造模第16天开始给药。采用ELISA检测鼻腔灌洗液、支气管肺泡灌洗液IL-4、IL-13、TGF-β;用RT-PCR检测鼻黏膜及肺组织XBP1 mRNA;用HE染色评价肺组织炎症情况。结果与正常对照组比较,模型组鼻腔灌洗液、支气管肺泡灌洗液及鼻黏膜、肺组织XBP1 mRNA指标明显升高(P<0.01);与模型组比较,醒鼻凝胶滴鼻剂6.88 mg/kg剂量组、13.76 mg/kg剂量组、27.52 mg/kg剂量组及雷诺考特组鼻腔灌洗液、支气管肺泡灌洗液的IL-4、IL-13、TGF-β,鼻黏膜的XBP1 mRNA指标明显降低(P<0.01);醒鼻凝胶滴鼻剂6.88 mg/kg剂量组、27.52 mg/kg剂量组,雷诺考特组及肺组织的XBP1 mRNA指标降低明显(P<0.01)。HE染色显示,与正常对照组比较,模型组豚鼠肺组织气道血管周围炎症细胞浸润明显;与模型组比较,醒鼻凝胶滴鼻剂干预后,醒鼻凝胶滴鼻剂6.88 mg/kg剂量组、13.76 mg/kg剂量组、27.52 mg/kg剂量组肺组织气道血管周围炎症细胞浸润减轻。结论醒鼻凝胶滴鼻剂可通过下调上气道包括鼻腔灌洗液、鼻黏膜等相关炎症因子的表达,减轻豚鼠鼻炎模型肺组织气道血管周围炎症,发挥治疗变应性鼻炎的作用,并能在一定程度上下调下气道相关的支气管肺泡灌洗液及肺组织相关炎症因子的表达,为醒鼻凝胶滴鼻剂在上下气道的变态反应性Th1/Th2细胞因子的作用机制研究提供了一定的实验参考数据。

Objective To observe the effect of the traditional Chinese medicine Xingbi Gelation Nasal Drops(醒鼻凝胶滴鼻剂)on nasal lavage fluid,bronchoalveolar lavage fluid IL-4,IL-13 and TGF-βin the upper and lower airway of allergic rhinitis guinea pigs and XBP1 in nasal mucosa and lung tissue,and the situation of the inflammation of lung tissue.Methods A total of 60 healthy guinea pigs were selected.After one week of adaptive feeding,the guinea pig model of allergic rhinitis was established by sensitization and stimulation of ovalbumin(OVA).The simple numbers and stratified random method were used.They were randomly divided into 6 groups:normal control group,model group,the traditional Chinese medicine Xingbi Gelation Nasal Drops 6.88 mg/kg,13.76 mg/kg and 27.52 mg/kg groups,Rhinocort group,10 rats in each group.And the administration started on the 16 th day of modeling.IL-4,IL-13 and TGF-βin nasal lavage fluid and bronchoalveolar lavage fluid were detected by ELISA.RT-PCR was used to detect the expression of XBP1 in nasal mucosa and lung tissue.HE staining was used to evaluate the inflammation of lung tissue.Results Compared with those of the normal control group,the levels of IL-4,IL-13 and TGF-βin nasal lavage fluid,bronchoalveolar lavage fluid and the indexes of XBP1 mRNA in nasal mucosa and lung tissues were increased significantly(P<0.01).Compared with those of the model group,the levels of IL-4,IL-13,TGF-βand XBP1 mRNA of the traditional Chinese medicine Xingbi Gelation Nasal Drops 6.88 mg/kg,13.76 mg/kg and 27.52 mg/kg groups and Rhinocort group.In nasal lavage fluid,bronchoalveolar lavage fluid and nasal mucosa were decreased significantly(P<0.01).The level of XBP1 mRNA in lung tissue of the traditional Chinese medicine Xingbi Gelation Nasal Drops 6.88 mg/kg and 27.52 mg/kg groups and Rhinocort group were decreased significantly(P<0.01).HE staining showed that compared with those of the normal control group,inflammatory cells infiltrated around the airway of guinea pigs in allergic rhinitis model group was obvious.After the emergence of the traditional Chinese medicine Xingbi Gelation Nasal Drops,compared with those of the model group,the infiltration of inflammatory cells around the airway in guinea pigs of the traditional Chinese medicine Xingbi Gelation Nasal Drops 6.88 mg/kg,13.76 mg/kg and 27.52 mg/kg groups were reduced.Conclusion The traditional Chinese medicine Xingbi Gelation Nasal Drops can reduce allergic rhinitis by reducing the expressions of inflammatory factors such as nasal lavage fluid,nasal mucosa,reduce the inflammation around the airway vessels in the lung tissue of guinea pig rhinitis model,and to a certain extent,it can reduce the expressions of related inflammatory factors in bronchoalveolar lavage fluid and lung tissue related to the lower airway,and provide some experimental reference data for the study of the mechanism of allergic nasal Th1/Th2 cytokines in the upper and lower airway.