放射線引發口腔黏膜潰瘍急性期與復原期之發炎反應

Abstract

絕大多數的頭頸部癌症患者接受放射線治療後會產生副作用—口腔黏膜炎(oral mucositis)，其發生率高達八至九成。口腔黏膜炎指的是口腔黏膜紅腫、萎縮、潰瘍等現象，這會造成患者進食、吞嚥、說話等方面的困難，不但影響生活品質，還會使患者產生劇烈的疼痛感，甚至導致治療計畫中斷，增加患者於術後照護上的經濟負擔以及傷口持續感染的可能性，然而並沒有有效的藥物來治療或預防口腔粘膜炎。牛樟芝Antrodia Camphorata為台灣特有的真菌，生長在海拔200~2000公尺以上的山中，且只長於牛樟樹，取得十分不易。許多文獻指出牛樟芝具有抗癌的效果，此外也具有抗發炎、抗氧化以及免疫調節的能力，本實驗即在評估牛樟芝是否可以緩解放射線所引發的口腔黏膜炎。實驗以舌頭組織作為觀察對象，於照射放射線前五天開始每天餵食牛樟芝或水，再以分次劑量5 x 10 Gy或單次劑量25 Gy放射線照射B6小鼠口吻部誘發口腔黏膜炎，並於照射後不同時間點犧牲小鼠取下舌部組織。兩種劑量下皆可成功引發小鼠舌頭潰瘍，但5 x 10 Gy模式小鼠死亡率極高，僅能觀察急性期之變化；25 Gy模式則能觀察到體重、舌頭外觀、組織學及發炎反應在急性期與復原期之變化。此外，實驗結果發現恢復期時舌尖恢復速度較舌中快，而急性期時餵食牛樟芝小鼠之IL-1βmRNA表現量低於餵食水的老鼠。

Oral mucositis is a common side effect of radiotherapy of patients with head-and-neck cancer. Persistent swelling, ulceration and atrophy of oral mucosa causes extreme discomfort, affects nutritional intake, and reduces patient quality of life. In addition, it increases the use of health resources, leads to oral and systemic infections as well as interrupts therapy. There are a lot of treatments for oral mucositis; unfortunately, the recommend treatment seems palliative. Antrodia camphorate (AC), a well-known Chinese folk medicine, is a fungal parasite on the inner cavity of the endemic species Cinnamomum kanehirae which only grows at an altitude of 200~2000 m in Taiwan. Many studies reveal that AC possesses extensive pharmacological effects, such as anti-cancer, anti-oxidant, immunomodulatory and anti-inflammatory activities. Hence, our specific aim is to evaluate whether AC can ameliorate radiation-induced oral mucositis. The changes of appearance, histology and immunology in both acute and recovery phase indicated we successfully established an oral mucositis mouse model by 25 Gy irradiation dose. Furthermore, our data suggested the tongue tip recovered more quickly than the tongue middle in recovery phase, and AC fed mice expressed lower IL-1βmRNA level than control mice in acute phase.