金針菇免疫調節蛋白 FIP-fve 在嗜中性氣喘之研究

The Effect of FIP-fve on neutrophilic asthma in mouse model

潘蕙嫻(Hui-Hsien Pan)

指導教授 ： 呂克桓

共同指導教授 ： 柯俊良(Jiunn-Liang Ko)

中山醫學大學/醫學院/醫學研究所/博士(2021年)

https://doi.org/10.6834/csmu202100043

摘要

研究目的：本研究旨在研究金針菇萃取物FIP-fve是否改善嗜中性氣喘動物模式，OVA/complete Freund’s adjuvants (CFA)致敏動物模式的表現，不管是在氣道高反應性的程度、第一型輔助T細胞(Th1)、第二型輔助T細胞(Th2)、上皮細胞和嗜中性球相關的細胞激素高低，或者氣道中發炎細胞數目及病理切片上發炎的程度，都是我們探討的項目。
研究方法及資料：我們用BALB/c 母鼠來進行試驗。首先在第1、2、3天腹腔注射OVA/CFA，然後在第14、17、21、24、27天，給予鼻腔OVA刺激。氣道高反應性的程度是用Buxco非侵入式呼吸道機制檢測系統來做測量，細胞激素是用ELISA的方式來做測定，發炎細胞用Liu’s stain 劉氏染色法來作染色，而氣道發炎的病理切片則是用hematoxylin and eosin stain H E染色並進一步判讀。
研究結果：OVA/CFA刺激可以誘發動物鼠的氣道高反應性、高IgE、高發炎細胞浸潤特別是嗜中性球以及細胞激素IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IL-17, IL-25, IL33和TGF-β的增加。和OVA/ALUM刺激鼠比較，OVA/CFA刺激鼠有較高的IL-6, IL-8, IL-10, IL-17, IL-25, IL-33和TGF-β。透過FIP-fve的治療，OVA/CFA刺激鼠的IL-12和IFN-γ增加，氣管管沖洗液中的IL-4, IL-5, IL-6, IL-8, IL-13, IL-17, IL-25, IL33和TGF-β減少。再者，FIP-fve減少肺部嗜中性白血球的浸潤。
結論與建議：OVA/CFA成功誘發出嗜中性氣喘的動物模式。根據我們的結果可以發現，FIP-fve除了可以改善以往觀念中以Th2為主的氣喘外，也可以改善嗜中性氣喘的表現和發炎反應。期望在不久的將來，FIP-fve可以被用來當作不同型別氣喘的替代療法。

關鍵字

嗜中性氣喘 ； 金針菇免疫調節蛋白FIP-fve ； 動物模式

並列摘要

Objective：To investigate whether FIP-fve could improve asthma in an OVA/complete Freund’s adjuvants (CFA) sensitized model, a neutrophilic asthma animal model, either in the degree of airway hyperresponsiveness (AHR), the level of the Th1, Th2, epithelial cell or neutrophil associated cytokines, the inflammatory cell count or the pathological section of inflammation.
Materials and methods：We used female BALB/c mice and sensitized them intraperitoneally with OVA/CFA on day 1, 2 and 3. On day14, 17, 21, 24 and 27, they were challenged with intranasal OVA. The AHR was detected by BUXCO, inflammatory cells were stained with Liu’s stain, the cytokines were detected by using ELISA and the airway inflammation was analyzed with H E stain.
Results：According to the results, OVA/CFA sensitization could induce AHR, high level of IgE, inflammatory cells especially neutrophils infiltration in the lung, and airway inflammation. IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IL-17, IL-25, IL33 and TGF-β were increased in the OVA/CFA sensitized mice. However, the higher cytokines in OVA/CFA sensitized mice than in OVA/Alum sensitized mice were IL-6, IL-8, IL-10, IL-17, IL-25, IL-33 and TGF-β. OVA/CFA sensitized mice treated with FIP-fve not only increased IL-12 and IFN-γ, but also decreased IL-4, IL-5, IL-6, IL-8, IL-13, IL-17, IL-25, IL-33 and TGF-β in the BALF. Moreover, FIP-fve significantly decreased neutrophil infiltration in the lung.
Conclusions：The OVA/CFA model induced neutrophilic asthma successfully. Based on our results, FIP-fve could improve not only Th2-dominant asthma, but also neutrophil-dominant asthma. Therefore, FIP-fve can be considered as a novel supplementary drug for asthma or allergies.

並列關鍵字

neutrophilic asthma ； FIP-fve ； mouse model

參考文獻

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