口服益生菌LGG預防及改善致敏小鼠之研究

Study on prevention and improvement of sensitization mices with oral Lactobacillus rhamnosus GG

陳芃均(Peng-Chun Chen)

指導教授 ： 呂克桓 ； 李宣信

中山醫學大學/健康管理學院/公共衛生學系碩士班/碩士(2011年)

摘要

氣喘是一個常見的慢性呼吸道疾病，隨著時間其盛行率也逐年上升，許多研究開始開發新的藥物來治療氣喘。其中以益生菌來預防或改善過敏疾病是一種新的概念，它能改善腸內微生物的平衡且調節腸胃道的菌群、調節過敏性病患腸道內的免疫機制，進而減緩炎症的反應及促進黏膜耐受性。而本研究探討益生菌之菌株為Lactobacillus rhamnosus GG（LGG），根據過去研究指出LGG會影響免疫反應，還可刺激免疫系統產生IFN-γ進而抑制Th2發炎細胞激素而減緩發炎情形。
本研究利用雞卵蛋白（chicken ovalbumin, OVA）誘發BALB/c母鼠產生致敏的現象。將小鼠隨機分為對照組（normal control, NC組）、致敏組（positive control, PC組）、前給LGG組（pre-LGG組）及後給LGG組（post-LGG組）4組。在實驗進程中，NC組於全程實驗中給予生理食鹽水代替方式；其餘三組於第1天至第3天及第14天以OVA腹腔注射致敏，並分別在第14、17、21、24及27天給予鼻腔吸入致敏。另外，預防和改善氣喘組別為pre-LGG組及post-LGG組分別於1至14天給予LGG，進而探討LGG對致敏小鼠氣喘之預防效果，另一則於第14至27天給予LGG，此意義是探討LGG對致敏小鼠氣喘之改善效果。
本研究結果發現利用OVA致敏小鼠是具有明顯呼吸道發炎的症狀，呼吸道發炎是由methacholine刺激後所獲得，並透過致敏小鼠血清（serum）及肺泡沖洗液（bronchoalveolar lavage fluid, BALF）中發現相關細胞激素如IgE、IL-4、IL-10有明顯的增加，而給予口服LGG之兩組，IFN-γ、IgG2a及TGF-β均有明顯的增加，而IgE、IL-4、IL-10均有明顯減少之趨勢。本研究發現口服LGG，不論是pre-LGG組或post-LGG組對於OVA致敏小鼠呼吸道炎症均可有預防及改善的效果，因此，LGG於呼吸道系統中扮演重要的角色，若在嬰幼時期給予口服LGG，進而促進腸道成熟調節免疫機制，未來能成為預防過敏性疾病的替代方式。

關鍵字

氣喘 ； Lactobacillus rhamnosus GG ； 益生菌 ； 呼吸道過度反應 ； IFN-γ

並列摘要

Asthma is one of the common chronic airway diseases, the prevalence of asthma has increased dramatically. Previous studies had developed new drugs to prevent or improve for asthma. In the present study, Lactobacillus rhamnosus GG（LGG）to prevent or treatment allergy is a new concept, it could improve balance of intestinal microbial and regulate allergic patient with immune system in intestinal and then reduce inflammation response and promote mucosal tolerance. This study explore Lactobacillus rhamnosus GG(ATCC 53103) was provided by previously study suggest LGG have been shown to modulate the immune system, also stimulate Th1 cytokines such IFN-γ can suppress Th2 inflammatory cytokines responses and reduce inflammation.
In the present study that airway inflammation was induced by ovalbumin（OVA）in BALB/c female mice. Experimental animals were divided into four groups：(1) normal control, (2) positive control, (3) pre-LGG, (4) post-LGG. In the experimental process, mices were received only saline in normal control group. Another groups not only have intraperitoneal OVA-induced asthma on days 1 to 3 and 14 but also have intranasal OVA on days 14, 17, 21, 24 and 27. In addition, pre-LGG and post-LGG on days 1 to 14 and days 14 to 27 to investigate the preventive and improvement effect of asthma mice , respectively.
This study represents that the immune effect of OVA on allergen-induced sensitization and development of airway inflammation as well airway hyperresponsiveness. Airway hyperresponsiveness to methacholine was observed in OVA-induced mice model of asthma. Both pre-LGG and post-LGG groups, cytokines such as IgE、IL-4、IL-10 in serum and bronchoalveolar lavage fluid（BALF）were surpressed significantly, anti-inflammatory cytokines such as IFN-γ、 IgG2a and TGF-β also increased significantly.
Our result suggested that oral LGG could provide prevent and improve effect on OVA-induced airway inflammation and as a result, LGG is regarded to play a major role in the airway system. Oral LGG during early infancy might promote maturation of the immune system. This indicated that LGG might be a new alternative therapy for allergic airway disease in the future.

並列關鍵字

Asthma ； Lactobacillus rhamnosus GG ； probiotics ； AHR ； IFN-γ

參考文獻

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