目的 观察玉屏风散对变应性鼻炎（AR）模型大鼠细胞自噬及炎症因子的影响,探索玉屏风散改善AR的潜在作用机制。方法 将Sprague Dawley大鼠随机分为正常对照组、AR模型组、玉屏风散组（24 mg·kg-1）、酮替芬组（阳性对照,0.9 mg·kg-1）、玉屏风散（24 mg·kg-1）+雷帕霉素（自噬诱导剂,1 mg·kg-1）组,每组10只。正常对照组给予200 mg·kg-1生理盐水,其余各组以卵清蛋白和氢氧化铝建立AR模型。记录AR大鼠鼻炎行为学症状并量化评分;采用免疫印迹和免疫荧光检测大鼠鼻黏膜自噬效应蛋白Beclin1的表达;ELISA检测大鼠鼻腔灌洗液和血清中干扰素γ（INF-γ）、白细胞介素-5（IL-5）、白细胞介素-13（IL-13）、免疫球蛋白E（IgE）及白细胞介素-4（IL-4）水平。结果 与正常对照组比较,AR模型组大鼠鼻腔灌洗液和血清中IL-5、IL-13、IgE和IL-4水平升高（P<0.01）,INF-γ水平降低（P<0.01）;与AR模型组比较,玉屏风散组和酮替芬组大鼠鼻腔灌洗液和血清中IL-5、IL-13、IgE和IL-4水平减少（P<0.01）,INF-γ水平升高（P<0.01）;Western Blot结果显示,与正常对照组比计较,AR模型组自噬相关蛋白Beclin1表达显著增加（P<0.05）;与AR模型组比较,玉屏风散组和酮替芬组Beclin1蛋白表达显著减少（P<0.01）;免疫荧光结果显示,与玉屏风散组比较,玉屏风散组+雷帕霉素组Beclin1蛋白表达显著增加,大鼠鼻腔灌洗液和血清中IL-5、IL-13、IgE和IL-4水平显著增加（P<0.01）,INF-γ水平明显减少（P<0.01）,大鼠鼻炎行为学评分显著增加（P<0.01）。结论 玉屏风散对AR具有良好疗效,其潜在作用机制与细胞自噬密切相关。
Abstract
Objective To observe the effects of Yupingfeng San on autophagy and inflammatory factors in allergic rhinitis (AR) model rats, and explore the potential mechanism of Yupingfeng San in improving AR. Methods Sprague Dawley rats were randomly divided into a normal control group, an AR model group, a Yupingfeng San group (24 mg·kg-1), a ketotifen group (positive control, 0.9 mg·kg-1), and a Yupingfeng San (24 mg·kg-1) + rapamycin (autophagy inducer, 1 mg·kg-1) group, with 10 rats in each group. The normal control group was given 200 mg·kg-1 physiological saline, while the other groups established AR models using ovalbumin and aluminum hydroxide. Record the behavioral symptoms of rhinitis in AR rats and quantify the scores. Immunoblotting and immunofluorescence were used to detect the expression of Beclin1, an autophagy related protein, in rat nasal mucosa. ELISA was used to detect the levels of interferon-γ (INF-γ), interleukin-5 (IL-5), interleukin-13 (IL-13), immunoglobulin E (IgE) and interleukin-4 (IL-4) in nasal lavage fluid and serum of rats. Results Compared with the normal control group, the levels of IL-5, IL-13, IgE, and IL-4 in the nasal lavage fluid and serum of the AR model group rats were significantly increased (P<0.01), while the level of INF-γ was significantly decreased (P<0.01). Compared with the AR model group, the levels of IL-5, IL-13, IgE, and IL-4 in nasal lavage fluid and serum of rats in the Yupingfeng San group and Ketotifen group were significantly reduced (P<0.01), while the levels of INF-γ were significantly increased (P<0.01). Western blot results showed that compared with the normal control group, the AR model group showed a significant increase in the expression of autophagy related protein Beclin1 (P<0.05). Compared with the AR model group, the expression of Beclin1 protein was significantly reduced in the Yupingfeng San group and Ketotifen group (P<0.01). The immunofluorescence results showed that compared with the Yupingfeng San group, the Yupingfeng San + rapamycin group showed a significant increase in Beclin1 protein expression, a significant increase in IL-5, IL-13, IgE, and IL-4 levels in nasal lavage fluid and serum of rats (P<0.01), a significant decrease in INF-γ levels (P<0.01), and a significant increase in behavioral scores of rat rhinitis (P<0.01). Conclusions Yupingfeng San has good therapeutic effects on AR, and its potential mechanism is closely related to cellular autophagy.
关键词
变应性鼻炎 /
玉屏风散 /
细胞自噬 /
炎症因子 /
机制
Key words
Allergic rhinitis /
Yupingfeng san /
Autophagy /
Inflammatory factors /
Mechanism
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] Bernstein JA,BernsteinJS,MakolR,et al. Allergic Rhinitis: A Review[J]. JAMA,2024,331(10):866-877.
[2] Wang XD,Zheng M,Lou HF,et al.An increased prevalence of self-reported allergic rhinitis in major Chinese cities from 2005 to 2011[J]. Allergy,2016,71(8):1170-1180.
[3] ToscaMA,TrinciantiC,NasoM,et al. Treatment of Allergic Rhinitis in Clinical Practice[J]. Curr Pediatr Rev,2024,20(3):271-277.
[4] 习媛,刘玉崟,廖超,等. 玉屏风加味鼻喷剂对变应性鼻炎大鼠IgE、sIgA及鼻黏膜病理的影响[J]. 河南中医,2023,43(5):693-699.
[5] 吴紫陆,李静波,王俊杰,等. 玉屏风散通过ROS/NLRP3/Caspase-1信号通路抗变应性鼻炎的作用机制[J]. 中国实验方剂学杂志,2023,29(24):1-10.
[6] Zhang X,Wang P,Dang Q,et al.Inflammatory cytokines and risk of allergic rhinitis: A Mendelian randomization study[J]. Cytokine,2024,177:156547.
[7] 廖超. 耳穴压丸配合辛芩颗粒治疗鼻鼽的临床疗效观察及证型相关性分析[D]. 成都:成都中医药大学,2017.
[8] 刘慧霞,肖志贤,吴跃,等. 变应性鼻炎(鼻鼽)中医辨证分型的研究进展[J]. 四川中医,2021,39(3):219-223.
[9] 吴孝政,黄高,刘杨,等. 玉屏风散对肺气虚证大鼠JAK1/STAT3通路及炎性反应的影响及相关机制研究[J]. 中华中医药学刊,2023,41(3):66-72.
[10] 宾骥,朱镇华,杨伟丽. 玉屏风散对肺气虚型变应性鼻炎豚鼠模型IL-4、IL-12、TNF-γ表达水平及鼻腔黏病理变化的影响[J]. 湖南中医药大学学报,2024,44(4):545-550.
[11] 史俊祖,王雪峰,冯欣然,等. 玉屏风散化学成分、药理作用、临床应用研究进展及质量标志物预测分析[J]. 辽宁中医药大学学报,2024,26(7):48-54.
[12] 林甦,黄敬之. 玉屏风散对变应性鼻炎模型大鼠TLR4/NF-κB信号通路的影响[J]. 中国中医药信息杂志,2018,2(12):49-52.
[13] 李鹏飞,丘琴,覃春萍,等. 玉屏风散的研究进展及质量标志物预测分析[J]. 中华中医药学刊,2024, 42(4):101-107.
[14] Lin Z,Long F,Kang R,et al.The lipid basis of cell death and autophagy[J]. Autophagy,2024,20(3):469-488.
[15] Xiao H,Tang AZ,Xu ML, et al.Mycobacterium vaccae attenuates airway inflammation by inhibiting autophagy and activating PI3K/Akt signaling pathway in OVA-induced allergic airway inflammation mouse model[J]. Mol Immunol,2024,173:30-39.
[16] Wang C,Zhuo JJ,Li WQ,et al.Role of autophagy and mitophagy of group 2 innate lymphoid cells in allergic and local allergic rhinitis[J]. World Allergy Organ J,2024,17(2):100852.
[17] Xiao C,Feng L,Yang W.Inhibition of dendritic cell autophagy alleviates the progression of allergic rhinitis by inhibiting Th1/Th2/Th17 immune imbalance and inflammation[J]. Histol Histopathol,2025,40(2):237-247.
[18] 向双娣,程林辉,喻强强,等. 益气温阳护卫汤调控PI3K/Akt/mTOR自噬途径治疗支气管哮喘大鼠机制[J]. 中国实验方剂学杂志,2023,29(14):38-46.
基金
黑龙江省省属高等学校基本科研业务费科研项目（2023-KYYWFMY-0035）
PDF(829 KB)
