【摘要】 目的：基于TRPM8、TRPA1介导的神经免疫交互调节，探讨鼻畅方雾化治疗冷刺激下变应性鼻炎（AR）的机制。方法：40只雌性SD大鼠随机分为空白组，空白+冷刺激组，模型组，模型+冷刺激组，激素组，鼻畅方低、中、高剂量组，每组5只。造模后雾化给药1周。观察大鼠行为学变化；HE染色观察鼻黏膜病理变化；免疫组化检测鼻黏膜TRPM8、TRPA1表达水平；Western Blot检测鼻黏膜NK-1R、CGRPR蛋白表达水平；透射电镜观察鼻黏膜肥大细胞超微结构；ELISA检测鼻灌洗液IgE、SIgA及血清IL-4、IL-13、IL-25、IL-33水平。结果：与模型+冷刺激组比较，各给药组大鼠AR症状缓解，笼内争斗行为、稀便次数减少，鼻黏膜上皮细胞脱落、纤毛掉落及固有层炎症细胞浸润改善；鼻畅方低、中剂量组TRPM8、TRPA1、NK-1R、CGRPR表达显著降低（P<0.05），鼻畅方中剂量组血管扩张现象缓解，鼻黏膜肥大细胞颗粒致密程度与内容物密度明显降低；鼻畅方高剂量组和激素组显著降低IgE、SIgA、IL-4、IL-13、IL-25、IL-33水平（P<0.05），鼻畅方中剂量组显著降低IgE、SIgA、IL-4、IL-25、IL-33水平（P<0.05），鼻畅方低剂量组显著降低SIgA、IL-4水平（P<0.05）。结论：鼻畅方雾化可改善大鼠冷刺激下AR，其机制可能与抑制TRPM8、TRPA1表达，调控AR的鼻黏膜神经源性炎症有关。更多还原

【Abstract】 Objective: To explore the mechanism of Bichang Formula nebulization in the treatment of allergic rhinitis(AR) under cold stimulation based on the neuroimmune interactive regulation mediated by TRPM8 and TRPA1. Methods: A total of 40 female SD rats were randomly divided into blank group, blank+cold stimulation group, model group, model+cold stimulation group, hormone group, and low-, medium-and high-doses group of Bichang Formula, with 5 rats in each group. Drug was administered by nebulization for one week after modeling. The behavioral changes of rats were observed, the pathological changes of nasal mucosa were observed by HE staining, the expression levels of TRPM8 and TRPA1 in nasal mucosa were detected by immunohistochemistry, the expression levels of NK-1R and CGRPR in nasal mucosa were detected by Western Blot, the ultrastructure of mast cells in nasal mucosa was observed by transmission electron microscope, the levels of IgE, SIgA in nasal lavage fluid and IL-4, IL-13, IL-25 and IL-33 in serum were detected by ELISA. Results: Compared with the model+cold stimulation group, the AR symptoms of rats in each treatment group were relieved, fighting behavior in the cage and the frequency of loose stools were reduced, nasal mucosal epithelial cell shedding, cilia falling, and inflammatory cell infiltration in the lamina propria were improved. The expressions of TRPM8, TRPA1, NK-1R and CGRPR were significantly decreased in low-and medium-dose groups of Bichang Formula(P<0.05). In medium-dose group of Bichang Formula, blood vessel dilation was relieved, and the increase in mast cell granule density and content density under cold stimulation was inhibited. The levels of IgE, SIgA, IL-4, IL-13, IL-25, and IL-33 were significantly decreased in high dose group of Bichang Formula and hormone group(P<0.05), the levels of IgE, SIgA, IL-4, IL-25 and IL-33 were significantly decreased in medium dose group of Bichang Formula(P<0.05), and the levels of SIgA and IL-4 were significantly decreased in low dose group of Bichang Formula(P<0.05). Conclusion: Bichang Formula nebulization can improve AR under cold stimulation in rats. The mechanism may be related to the inhibition of TRPM8 and TRPA1 expression and the regulation of nasal mucosal neurogenic inflammation of AR.更多还原