口服金針菇免疫調節蛋白預防及治療致敏小鼠之研究

近年來氣喘的發生率持續的快速增加，因此針對氣喘所做的研究也愈來愈多而治療過敏氣喘的新藥也不斷的被開發出來，而目前對於氣喘的治療藥物多以症狀緩解為主，此外在未來則是以了解氣喘的完整機制以及發展有效抑制氣喘發炎反應之藥物為主要目標。目前針對金針菇免疫調節蛋白(fungal immunomodulatory protein-fve, FIP-fve)的研究指出，金針菇免疫調節蛋白是由新鮮金針菇萃取而來，而此蛋白具有抗腫瘤、抗病毒、抗菌以及降低膽固醇等活性，另外研究中亦顯示此蛋白具有刺激人類周邊血淋巴球細胞以及增強免疫細胞中的細胞激素如IL-2 與IFN-γ。因此在本研究中我們想了解金針菇免疫調節蛋白對於致敏小鼠模型中呼吸道發炎反應的影響。本研究是使用BALB/c母鼠以雞卵蛋白 (chicken ovalbumin, OVA)誘發小鼠產生致敏的現象，實驗中在第1天至第3天及第14天進行OVA腹腔注射進行致敏作用並於第14、17、21、24及27天進行OVA鼻腔吸入動作，此動物實驗模式已建立完成。此外本研究將致敏小鼠隨機分為2組，一組將FIP-fve餵食於實驗進程第0天至第14天此組的意義為探究FIP-fve對於氣喘疾病預防的效果，另一組則為實驗進程第14天至第27天餵食致敏小鼠FIP-fve此組別則為探究FIP-fve對於氣喘的治療效果。而在本研究的對照組則是以生理實鹽水進行並做為非致敏小鼠之對照。根據研究結果顯示，OVA致敏小鼠具有的明顯呼吸道發炎反應現象會經由前後給予口服FIP-fve而受到抑制。呼吸道過度反應現象是藉由methacholine刺激致敏小鼠後所獲得。而無論是前或後給予口服FIP-fve都能回復呼吸道過度反應現象。另外在致敏小鼠的血清及肺泡沖洗液中(bronchoalveolar lavage fluid, BALF)其IgE、IL-4、IL-10都有明顯增加而IFN-γ與TGF-β則有明顯減少的現象，但這些現象在前後給予口服FIP-fve的致敏小鼠中都會獲得改善。本研究可發現口服FIP-fve對於OVA引起的呼吸道發炎反應具有抗發炎的效果，而口服FIP-fve對於過敏性呼吸道疾病可能是一項很好的替代性治療方式。

關鍵字

氣喘；慢性呼吸道發炎；嗜伊紅性白血球；金針菇免疫調節蛋白

並列摘要

The incidence of asthma has increased substantially in the last two decades. New medication is developed rapidly in recent years to apply to allergic asthma, since lots of people have investigated about the issue. However, now existing drugs just offer partial relief of symptoms in such disease. The goal of feature is to understand the complicated mechanism of asthma, and develop more effective drugs for suppressing the inflammatory response in asthma. The golden needle mushroom, Flammulina velutipes, and extracts, possess immunomodulatory, anti-tumor, anti-viral, anti-fungal and cholesterol-lowering activities. A major fruiting body protein, designated Fve or FIP-fve, was isolated and very likely plays a significant role in the mushroom’s immunomodulating effects. It stimulates mitogenesis of human peripheral lymphocytes and enhances the transcription of interleukin-2 (IL-2), interferon-g (IFN-γ). We examined the role of agent of edible golden needle mushroom extract FIP-fve in a mouse asthma model after allergen-induced chronic airway inflammation. Female BALB/c mice, after intraperitoneal ovalbumin (OVA) sensitization on days 1 to 3 and 14, received intranasal OVA on days 14, 17, 21, 24 and Days 27. The mouse asthma model with airway inflammation by airway mucus release and infiltration by eosinophils was set up. The sensitized mice were divided into 2 groups. One group, the sensitized mice will be fed with FIP-fve on days0 to days14 meaning prevention. Another group, the sensitized mice will be fed with FIP-fve on days14 to days28 meaning treatment. In this mouse asthma model, normal saline was used as a positive control. The non-sensitized mice were used as a negative control. The results show that OVA-sensitized mice developed a significant airway inflammatory response that was inhibited by pre- and post treated with FIP-fve. Airway hyperresponsiveness to methacholine was observed in OVA-sensitized mice. Both pre- and post-treated with FIP-fve reversed airway hyperresponsiveness. An increase in IgE, IL-4, IL-10 and a decrease in IFN-γ, TGF-βin bronchoalveolar lavage fluid (BALF) and sera were found in OVA-sensitized mice, but were reversed by both pre- and post- treated with FIP-fve. From this study, oral FIP-fve could produce an anti-inflammatory effect on OVA-induced airway inflammation and oral FIP-fve might be a good alternative therapy for allergic airway disease.

並列關鍵字

Asthma ； Chronic airway inflammation ； Eosinophil ； FIP-fve

參考文獻

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口服金針菇免疫調節蛋白預防及治療致敏小鼠之研究

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