木犀草素通过TRPV1/ERK相关信号通路减轻OVA诱导的过敏性鼻炎合并哮喘综合征小鼠的神经源性炎症

文献信息

中文摘要

目的： 过敏性鼻炎合并哮喘综合征（CARAS）是一种常见的慢性过敏性呼吸系统疾病，涉及神经-免疫相互作用失调和神经源性炎症。木犀草素（LUT）具有显著的抗炎和抗氧化活性。然而，其在CARAS中的作用及潜在机制尚不清楚。本研究旨在确定在CARAS气道激发阶段给予LUT的效果及其与TRPV1/ERK信号通路的关联。
方法： 采用BALB/C小鼠建立卵清蛋白（OVA）诱导的CARAS模型并给予LUT。通过计数鼻痒和打喷嚏次数评估鼻部症状。进行HE和甲苯胺蓝染色以确定组织病理学变化。测定支气管肺泡灌洗液（BALF）中的总细胞和分类细胞计数。通过ELISA试剂盒检测组胺、MCP-1、P物质（SP）、CGRP以及Th1/Th2/Th17相关细胞因子的水平。此外，通过免疫荧光染色和Western blotting检测TRPV1和p-ERK表达水平。
结果： 我们的研究表明，与模型组相比，LUT给药显著降低了CARAS小鼠的打喷嚏频率、鼻痒行为和血清OVA特异性IgE水平。组织病理学分析表明，LUT给药减少了鼻黏膜和肺组织中的炎症细胞积聚和组织学评分，并与BALF中炎症细胞计数减少相关。此外，LUT给药降低了两种组织中的肥大细胞密度。LUT给药后，血清组胺和MCP-1水平以及肺组织中IL-4、IL-5、IL-13、IL-17A和IFN-γ水平也降低。LUT给药还降低了血清和BALF中SP和CGRP水平。此外，LUT给药降低了鼻黏膜和肺组织中的TRPV1表达和p-ERK水平。
结论： LUT给药可减轻OVA诱导的CARAS小鼠的过敏和炎症反应，这可能与TRPV1/ERK信号通路有关。

英文摘要

OBJECTIVE: Combined Allergic Rhinitis and Asthma Syndrome (CARAS), a common chronic allergic respiratory disease, involves dysregulated neuro-immune interactions and neurogenic inflammation. Luteolin (LUT) has significant anti-inflammatory and antioxidant activities. However, its effects and underlying mechanism in CARAS remain unclear. This study aims to determine the effects of LUT administration during the airway challenge phase of CARAS and its association with TRPV1/ERK signaling.
METHODS: BALB/C mice were used to establish an ovalbumin (OVA)-induced CARAS model and LUT was administered. The nasal symptoms were evaluated by counting the number of nasal scratching and sneezing. HE and toluidine blue staining were performed to determine the histopathological changes. Total and differential cell counts in bronchoalveolar lavage fluid (BALF) were determined. The levels of histamine, MCP-1, substance P (SP), CGRP and Th1/Th2/Th17-related cytokines were detected by ELISA kit. Besides, TRPV1 and p-ERK expression levels were measured by immunofluorescence staining and Western blotting.
RESULTS: Our study indicated that LUT administration significantly reduced sneezing frequency, nasal scratching behavior, and serum OVA-specific IgE level in CARAS mice compared to the model group. Histopathological analysis demonstrated that LUT administration reduced inflammatory cell accumulation and histological scores in the nasal mucosa and lung tissues and was associated with reduced inflammatory cell counts in BALF. In addition, LUT administration reduced mast cell density in both tissues. Serum histamine and MCP-1 levels and pulmonary levels of IL-4, IL-5, IL-13, IL-17A, and IFN-γ were also reduced following LUT administration. LUT administration also reduced serum and BALF levels of SP and CGRP. Furthermore, LUT administration reduced TRPV1 expression and p-ERK levels in the nasal mucosa and lung tissue.
CONCLUSION: LUT administration attenuates allergic and inflammatory responses in OVA-induced CARAS mice, which may be associated with TRPV1/ERK signaling.