類固醇皂苷元diosgenin促進卵白蛋白免疫小鼠表現抗原專一性IgG2a抗體和伽馬干擾素

Diosgenin, a steroidal sapogenin, enhances antigen-specific IgG2a and interferon-γ expression in ovalbumin-sensitized BALB/c mice

官照晴(Chio-Chin Kuan)

指導教授 ： 詹東榮

國立臺灣大學/生物資源暨農學院/獸醫學研究所/碩士(2006年)

https://doi.org/10.6342/NTU.2006.02826

摘要

山藥在傳統中醫學上被認為具有減輕疲勞、安定神經、止咳、化痰、抗發炎、抗氣喘、治療腹瀉等功效，但大多缺乏科學證實。在亞洲國家，山藥被視為滋養強身增進免疫力的健康食品，廣被一般民眾食用。Diosgenin（DIO）為山藥含量最豐富的皂苷元，並且具有多種的生物活性，如降血糖、抗腫瘤、增進膽汁排放等，本研究主要目的在探討DIO對卵白蛋白敏感化及氣霧刺激之BALB/c鼠之全身系統性抗體生成反應及脾臟細胞表現細胞激素的作用，並進一步探討其對Th細胞分化的可能影響。DIO的給予為每日一次管餵200或400 毫克/公斤體重（DIO 200和DIO 400），共給予34天，餵藥期間以卵白蛋白(ovalbumin)腹腔注射敏感化兩次、氣霧刺激三次，血清抗體以ELISA檢測共兩次，第一次是在小鼠第一次卵白蛋白敏感化兩週後，第二次則在最後ㄧ次卵白蛋白氣霧刺激48小時之後。第一次的血清結果顯示，DIO 200降低卵白蛋白專一性抗體IgE含量，DIO 200及DIO 400降低整體IgE的生成；而第二次的血清結果顯示，DIO 200及DIO 400對卵白蛋白專一性的抗體IgG2a生成有明顯的促進作用。分析脾臟細胞的細胞激素表現，Th1細胞激素IFN-γ的蛋白質分泌和mRNA表現在DIO餵食的小鼠皆明顯高於對照組，進一步以RT-PCR去偵測調控Th1分化的轉錄因子T-bet的mRNA表現，也有上升的趨勢。然而DIO對Th2細胞激素IL-4的分泌和mRNA的表現並無作用，偵測上游Th2的轉錄因子GATA-3及細胞激素抑制蛋白SOCS3的mRNA表現，也未受到DIO的影響。在肺臟組織中的IL-4 mRNA的表現、病理組織切片炎症細胞浸潤情形及黏液的生成也都顯示DIO不具有降低呼吸道局部炎症反應的作用。
综合上述結果，DIO對早期的抗體IgE生成有所調控，但在晚期的卵白蛋白加強免疫的抗體IgE和Th2分化、細胞激素相關的調控上並無活性。然而DIO具有增加抗原專一性抗體IgG2a的生成和IFN-γ表現的作用，DIO並具有促進Th1細胞分化的活性，使Th1/Th2平衡朝向Th1的趨勢，本研究的結果指出山藥的皂苷元成分在活體動物模式具有增進某些免疫反應的活性。

關鍵字

山藥 ； 植物固醇 ； 免疫調節 ； T細胞 ； 細胞激素 ； 基因表現

並列摘要

Chinese yam is a commonly used herb in Taiwan and several other Asian countries. The most abundant steroidal sapogenin contained in the root of Chinese yam is diosgenin (DIO), which has been shown to exhibit a number of biological activities. The objective of the present study was to investigate the effect of DIO on antibody production and T-cell reactivity in BALB/c mice sensitized with ovalbumin (OVA) and subsequently challenged with aerosolized OVA. Mice were administered with DIO (200 or 400 mg/kg) by gavage daily for 34 days. Serum samples were obtained 2 weeks after each OVA sensitization, and mice were sacrificed 2 days post the OVA challenge. Diosgenin treatment attenuated the production of OVA-specific IgE and total IgE in serum obtained after the 1st Ova sensitization, but significantly enhanced IgG2a in serum after the 2nd sensitization. In parallel with the enhancement of anti-OVA IgG2a, the expression of the Th1 cytokine IFN-gamma and T-bet transcription factor in splenocyes isolated from DIO-treated mice was markedly elevated, whereas the expression of the Th2 cytokine IL-4 and GATA-3 transcription factor was unaffected. Accordantly, DIO treatment did not affect the steady state mRNA expression of IL-4 in the lungs of mice sensitized and challenged with OVA. Moreover, the production of mucin and infiltration of inflammatory cells in the lungs of OVA-sensitized and challenged mice were not affected by DIO treatment. Taken together, the data suggest that exposure of mice to DIO results in modulation of the immune response toward Th1 direction in response to OVA sensitization, whereas Th2 cell-derived immunity and allergic airway reactions were relatively unaltered. The present study is the first report to show the immunomodulatory activity of DIO in vivo. Our data provide the evidence that intake of DIO, the major sapogenin contained in Chinese yam, may up-regulate certain aspects of immunity due to the enhancement of IFN-gamma expression and Th1 differentiation.

並列關鍵字

Chinese yam ； diosgenin ； steroidal sapogenin ； T cell ； cytokine ； gene expression

參考文獻

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