基于过敏性鼻炎免疫途径探讨镰形棘豆总黄酮调控Toll样受体的作用机制  

Regulation Mechanism of the Total Flavone in Oxytropis Falcate Bunge on Toll-like Receptor Based on Allergic Rhinitis Immune Pathway

作　　者：郭敏[1,2,3] 李晓东 黄聪琳[1] 王晓琳[1,2] 顾立萍[2] GUO Min;LI Xiaodong;HUANG Conglin;WANG Xiaolin;GU Liping(Gansu Provincial Hospital of TCM,Lanzhou 730050 Gansu,China;Gansu Provincial Academy of TCM,Lanzhou 730050 Gansu,China;College of Pharmacy,Gansu University of Chinese Medicine,Lanzhou 730000 Gansu,China)

机构地区：[1]甘肃省中医院,甘肃兰州730050 [2]甘肃省中医药研究院,甘肃兰州730050 [3]甘肃中医药大学药学院,甘肃兰州730000

出　　处：《中药新药与临床药理》2021年第11期1657-1662,共6页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：甘肃省引导科技创新发展竞争性专项(甘财科[2017]168号);甘肃省卫生行业专项(GSWSKY2018-46);甘肃省中医药科研项目(GZK-2018-54,GZK-2018-55)。

摘　　要：目的基于过敏性鼻炎(AR)免疫途径探讨镰形棘豆总黄酮调控Toll样受体的作用机制。方法将50只Wistar大鼠随机分为5组,分别为空白组、模型组、西替利嗪组及镰形棘豆总黄酮组低、高剂量组。除空白组外,其余4组大鼠采用卵蛋白(OVA)制作过敏性鼻炎模型,西替利嗪组及镰形棘豆总黄酮组低、高剂量组分别给予西替利嗪(1 mg·kg^(-1))、镰形棘豆总黄酮(0.47、1.87 g·kg^(-1),按生药计)灌胃2周。HE、免疫组化染色观察各实验组大鼠鼻黏膜组织变化;ELISA法测定血清中转化生长因子(IFN)-γ、白细胞介素(IL)-2及IL-4含量;Western Blot法检测鼻黏膜中TLR2、TLR4蛋白表达。结果与空白组比较,模型组行为学评分增加(P<0.01),差异有统计学意义;鼻黏膜纤毛及上皮细胞脱落,基底膜增厚,炎性细胞浸润,TLR2、TLR4阳性细胞增多;血清IL-2(P>0.05)、IFN-γ含量降低(P<0.05)、IL-4含量升高(P<0.05);鼻黏膜TLR2、TLR4蛋白的表达增强(P<0.01),差异有统计学意义。与模型组比较,西替利嗪组(P<0.01)、镰形棘豆总黄酮低剂量组(P<0.05)、镰形棘豆总黄酮高剂量组(P<0.01)行为学评分均降低,差异有统计学意义;各药物组鼻黏膜组织结构均改善、炎性浸润减少、TLR2、TLR4阳性细胞减少;西替利嗪组、镰形棘豆总黄酮高剂量组血清INF-γ含量升高(P<0.05)、IL-4含量降低(P<0.05),差异有统计学意义;镰形棘豆总黄酮低剂量组血清IL-2和INF-γ含量升高,IL-4含量降低,但差异无统计学意义(P>0.05);西替利嗪组、镰形棘豆总黄酮高剂量组鼻黏膜TLR2、TLR4蛋白表达减弱(P<0.05),差异有统计学意义。结论镰形棘豆总黄酮对卵清蛋白诱导的过敏性鼻炎具有改善作用且与剂量正相关,可能是通过调节TLR2和TLR4蛋白表达及Th1/Th2平衡影响机体免疫。Objective To explore the regulation mechanism of the total flavone in Oxytropis falcate Bunge(TFO)on Toll-like receptor based on allergic rhinitis(AR)immune pathway.Methods 50 Wistar rats were randomly divided into five groups:blank group(A),AR model group(B),cetirizine group(C),low-dose TFO group(D),highdose TFO group(E).Except group A,the other four groups were made AR models by ovalbumin(OVA).Group C,D and E were given cetirizine(1 mg·kg^(-1))and TFO(0.47,1.87 g·kg^(-1))by intragastric administration for 2 weeks,the histomorphologic changes in the nasal mucosa of rats were observed by HE and immunohistochemical staining.The serum levels of IFN-γ,IL-2 and IL-4 were detected by ELISA,and the expression of TLR2 and TLR4 in nasal mucosa was detected by Western Blot.Results Compared with group A,the behavioral score was increased in model groups(P<0.01).Desquamated nasal mucosa cilia and epithelial cells,thickened basement membrane and infiltrated inflammatory cells were observed.The positive rates of TLR2 and TLR4 increased,serum levels of IL-2(P>0.05),IFN-γ decreased(P<0.05),levels of IL-4 increased(P<0.05),and the expression of TLR2 and TLR4 in nasal mucosa increased significantly(P<0.01).Compared with group B,the behavioral scores of group C(P<0.01),group D(P<0.05)and group E(P<0.01)were all decreased.The tissue structure of nasal mucosa was improved,inflammatory infiltration was decreased,and the positive rates of TLR2 and TLR4 were decreased in each drug group.The levels of INF-γ in group C and group E were significantly increased(P<0.05),and the levels of IL-4 were significantly decreased(P<0.05).Moreover,the levels of IL-2 and INF-γ in group D were increased,and the levels of IL-4 were decreased(P>0.05).The expressions of TLR2 and TLR4 in the nasal mucosa of group C and group E were significantly decreased(P<0.05).Conclusion TFO can improve OVA-induced AR and the effect was positively correlated with the dose.It may affect the immune response by regulating the TLR2,TLR4 protein expression and Th1/Th2

关 键 词：镰形棘豆总黄酮 过敏性鼻炎 TOLL样受体 免疫功能 大鼠 

分 类 号：R285.5[医药卫生—中药学]