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標題: | 牛樟芝在放射線所引發口腔黏膜炎中的治療作用 Therapeutic effects of Antrodia camphorata on radiation-induced oral mucositis |
作者: | Yi-Ru Chen 陳怡如 |
指導教授: | 賈景山(Jean-San Chia) |
關鍵字: | 口腔黏膜炎,牛樟芝, Oral mucositis,Antrodia camphorata, |
出版年 : | 2014 |
學位: | 碩士 |
摘要: | 頭頸癌病人接受放射線治療後,會產生一種常見的副作用口腔黏膜炎,指的是口腔黏膜發炎、紅腫、潰瘍等現象,而口腔和咽喉的神經十分敏感,發炎會十分疼痛,無法言語,吞嚥困難,嚴重時只能靠靜脈注射供應水份及營養,影響癌症治療的結果。Reactive oxygen species及細胞激素 IL-1β、TNF-α常見於口腔黏膜潰瘍組織中,證明口腔黏膜炎是一種發炎相關疾病,但目前對於口腔黏膜炎的治療和預防效果都十分有限。Antrodia camphorata牛樟芝為台灣特有的真菌,牛樟芝具有抗癌、抗氧化和抗發炎的作用。餵食牛樟芝可抑制照射放射線所引發IL-1β反應在先前本實驗室所建立放射線引發口腔黏膜炎小鼠模式中,推測牛樟芝在口腔黏膜炎中扮演保護角色。Thalidomide為免疫調節藥物,具有抗癌、抗血管生成和免疫調節的作用,主要是透過降低TNF-α生成,而達到調節細胞激素的生成作用。Glutamine是具有抗氧化、免疫調節、提供能量特性的一種必需胺基酸,常見商品名為速養療,當作病人的營養添加劑,當病人服用glutamine可顯著降低口腔黏膜炎的嚴重性。因此本實驗將評估牛樟芝、thalidomide、glutamine這三種藥物是否可改善放射線引發的口腔黏膜炎。首先測試牛樟芝細胞毒性分析;第二是進行動物模型,分別以不同萃取方法牛樟芝 AC1和AC2、thalidomide、glutamine等四種藥物,針對口腔黏膜潰瘍的部位進行局部水敷,療效之評估方式為老鼠體重、舌頭外觀、生存率、舌頭發炎區塊計量等;第三是牛樟芝的高效液相色譜法分析。結果顯示,在牛樟芝濃度100 μg/ml以上對於人類舌癌鱗狀細胞株SAS具有細胞毒性,然而在正常細胞人類角質細胞株HaCaT則沒有細胞毒性;動物模式中發現,AC1、thalidomide、AC2可以有效緩解放射線誘發的體重下降;就舌頭外觀來看,AC1、thalidomide、AC2能讓發炎反應提早開始復原;就生存率來看,AC1、thalidomide能夠提高老鼠的存活率;就發炎區塊來看,thalidomide能在第十二和十四天有效減低發炎區塊,AC2能在第十四天有效減低發炎區塊,而AC1能使發炎趨勢減少,反之glutamine不具有緩解口腔黏膜炎之效果;高效液相色譜法分析發現,牛樟芝會隨著放置的時間增加而降解,因此每一次實驗都以新鮮泡製進行,另外,所使用之敷料為濾紙和紗布料,HPLC結果顯示,濾紙和紗布所吸收的成分一樣。綜合以上結果,牛樟芝和thalidomide能夠提供保護作用,有效減低口腔黏膜炎的嚴重性。 Oral mucositis (OM) is the most common side-effect of patients with head and neck cancer undergoing radiation therapy. OM induced painful and difficult swallowing often interferes the radiotherapy course of cancer. OM is an inflammation-associated disease due to reactive oxygen species and proinflammatory cytokine including IL-1β and TNF-α detected in mucositis tissue. However, clinical management has not efficiently prevented and treated OM. Antrodia camphorata (AC) is a unique medical fungus of Taiwan, and has anti-cancer, anti-oxidant and anti-inflammatory effects. Previously, oral administration of AC attenuated IL-1β response in radiation-induced oral mucositis (RIM) mouse model was established by our lab and we speculated AC plays a protective role in OM. Thalidomide is an immunomodulatory drug, which has anti-cancer, anti-angiogenic, immunomodulatory effects through its down-regulated effect on TNF-α. Glutamine is an anti-oxidant, with immune regulation, to provide the energy characteristics of the essential amino acids; the brand name is SYMPT-X Plain Glutamine as patient's nutritional additives. Oral administration of glutamine can significantly reduce severity of OM. Therefore, our specific aim is to evaluate the therapeutic effect of AC from two extraction methods, thalidomide and glutamine on RIM. Firstly, we test the cytotoxicity effect of AC in cell viability test. Secondly, we test the therapeutic effect in animal model. Finally, the ingredients of AC are analyzed by high performance liquid chromatography (HPLC). Our data discovered that higher concentration of AC had cytotoxic effects on human tongue squamous cell, SAS. In RIM, topical application of AC1, AC2 and thalidomide solution in mucositis site reduced radiation induced body weight loss and ulceration/redness in tongue. AC1 and thalidomide can improve mouse survival in RIM. But glutamine had no therapeutic effect. HPLC data showed the effects of AC degraded by the time passing; the ingredients in AC- absorbed filter paper and gauze are the same. In summary, out study found AC and thalidomide had therapeutic effect on radiation-induced mucositis. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/55991 |
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顯示於系所單位: | 口腔生物科學研究所 |
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