玉屏风散对变应性鼻炎模型大鼠TLR4/NF—κB信号通路的影响
2018-12-06林甦黄敬之
林甦 黄敬之
摘要:目的 观察玉屏风散对变应性鼻炎(AR)鼻黏膜上皮细胞TLR4/NF-κB信号通路的影响,探讨其作用机制。方法 采用卵清白蛋白致敏建立AR大鼠模型。实验大鼠随机分为正常组、模型组和玉屏风散低、中、高剂量组。采用AR行为学指标进行评分,HE染色观察大鼠鼻黏膜形态;ELISA测定大鼠血清白细胞介素(IL)-4、IL-5、IL-10、免疫球蛋白E(IgE)和干扰素-γ(IFN-γ)含量,Western blot、RT-PCR檢测大鼠鼻黏膜Toll样受体4(TLR4)和核因子(NF)-κB p65蛋白和基因的表达。结果 与正常组比较,模型组大鼠血清IL-4、IL-5、IgE含量显著升高,IL-10和IFN-γ含量显著降低(P<0.01),鼻黏膜TLR4、NF-κB p65蛋白和基因表达显著升高(P<0.01);与模型组比较,玉屏风散中、高剂量组大鼠血清IL-4、IL-5、IgE含量显著降低,IL-10和IFN-γ含量显著升高(P<0.05,P<0.01),鼻黏膜TLR4、NF-κB p65蛋白和基因表达显著降低(P<0.05,P<0.01)。结论 玉屏风散可能通过调节模型大鼠TLR4/NF-κB信号通路及相关炎性因子,而起到治疗AR的作用。
关键词:变应性鼻炎;玉屏风散;TLR4/NF-κB信号通路;免疫因子;大鼠
DOI:10.3969/j.issn.1005-5304.2018.12.013
中图分类号:R285.5 文献标识码:A 文章编号:1005-5304(2018)12-0048-05
Abstract: Objective To investigate the effects of Yupingfeng Powder on TLR4/NF-κB signaling pathway in allergic rhinitis nasal epithelial cells; To discuss its mechanism of action. Methods AR rat models were established by using ovalbumin sensitization. Experimental rats were randomly divided into normal group, model group and Yupingfeng Powder low-, medium- and high-dosage groups. After modeling, the AR behavioral index was used for scoring, and nasal mucosa by HE staining were observed. Serum IL-4, IL-5, IL-10, IgE and IFN-γ levels in rats were detected by ELISA. Western blot and RT-PCR were used to detect proteins and gene expressions of Toll-like receptor 4 (TLR4) and NF-κB p65 in nasal mucosa. Results Compared with the normal group, the contents of IL-4, IL-5, IgE and proteins and gene expressions of TLR4 and NF-κB p65 in the model group increased significantly, IL-10 and IFN-γ decreased significantly (P<0.01) and proteins and gene expressions of TLR4 and NF-κB p65 in nasal mucosa increased significantly (P<0.01); Compared with the model group, the contents of IL-4, IL-5 and IgE in Yupingfeng Powder medium- and high-dosage groups decreased significantly IL-10 and IFN-γ decreased significantly (P<0.05, P<0.01), and proteins and gene expressions of TLR4 and NF-κB p65 in nasal mucosa increased significantly (P<0.05, P<0.01). Conclusion Yupingfeng Powder has a certain therapeutic effect on AR by regulating the TLR4/NF-κB signaling pathway and inflammatory cytokines in model rats.
Keywords: allergic rhinitis; Yupingfeng Powder; TLR4/NF-κB signaling pathway; immune factor; rats
变应性鼻炎(allergic rhinitis,AR)又称过敏性鼻炎,是一种吸入变应原而导致的以鼻黏膜嗜酸性颗粒细胞、T淋巴细胞等多种炎性细胞浸润,免疫球蛋白E(immunoglobulin E,IgE)介导免疫细胞释放化学介质诱发的Ⅰ型变态反应炎性疾病,其主要临床特征是鼻痒、喷嚏、鼻分泌亢进和鼻黏膜肿胀等。AR发病与多种因素相关,病因复杂。目前大多数研究表明,AR病理生理变化主要由炎性介质引发,免疫细胞分泌炎症因子参与AR发病的复杂模式,但其发病机制尚未彻底阐明[1-2]。近年来随着人们生活方式和生活环境的改变,AR发病率呈逐年增加的趋势。本研究采用卵清白蛋白致敏建立AR大鼠模型,观察玉屏风散对AR鼻黏膜上皮细胞TLR4/NF-κB信号通路的影响,探讨其作用机制。
1 实验材料
1.1 动物
SPF级雄性Wistar大鼠50只,体质量250~300 g,上海斯莱克实验动物有限责任公司,动物许可证号SCXK(沪)2012-0002。饲养于室温(25 ℃)、相对湿度45%~55%环境,12 h/12 h明暗交替,常规喂养7 d。……
