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標題: 乳鐵蛋白、玻尿酸及自體血清眼藥水對兔角膜基質損傷癒合效果之比較
Comparison of lactoferrin, hyaluronic acid, and autologous serum eye drops on corneal stromal wound healing in rabbits
作者: 董盈資
Ying-Tzu Tung
關鍵字: 乳鐵蛋白
hyaluronic acid
autologous serum
corneal ulceration
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摘要: 角膜潰瘍為犬貓常見疾病,是一種有影響視覺、需要緊急處理的疾病。部分角膜潰瘍可以內科療法控制,然而部分病例會建議以外科手術治療,如結膜皮瓣與填補生物醫學材料。然而外科治療在臨床上會有一些使用限制,可能因為病患麻醉風險較高及費用相對昂貴等因素常不被飼主接受。目前多篇研究顯示在角膜淺層潰瘍使用乳鐵蛋白、玻尿酸或者是自體血清眼藥水能夠幫助角膜上皮癒合,然而對角膜基質的作用仍舊未知。本研究的目的為使用乳鐵蛋白、玻尿酸及自體血清眼藥水對兔子角膜基質潰瘍進行治療,比較對角膜損傷的治療效果。 實驗對象為2-3公斤雄性紐西蘭白兔,首先會將35隻兔子依照眼藥水隨機均分成5組,分別為乳鐵蛋白組、乳鐵蛋白陰性對照組、玻尿酸組、自體血清組及磷酸鹽緩衝溶液組,也就是空白對照組。實驗兔會先依照經濟合作暨發展組織的規範進行急性眼部刺激試驗,無異常再開始試驗。在單側角膜中央製造直徑8 mm、深度為375µm的傷口後,依照組別給予眼藥水,每天4次、每次一滴,持續4周。於誘導潰瘍後1、2、3、4、5、6、7、10、13、16、19、22、25、28天進行眼部臨床症狀及角膜潰瘍範圍的觀察,試驗終止時間為誘導潰瘍後第28天,實驗兔安樂死後取下眼球製作切片進行組織病理學檢查,測量角膜中央上皮與基質厚度、依照基質膠原排列與炎症細胞浸潤程度進行分級。結果,於急性眼部刺激試驗中,在給予眼藥水後1、24、48、72小時各組皆無發現角膜不透明度、虹彩病變、結膜充血及水腫。在誘導基質潰瘍後臨床症狀與潰瘍面積於各檢查時間點各組間無統計學上的顯著差異,組織學相關數值在各組間無統計學上的顯著差異。以整個試驗期間為基準,角膜潰瘍的有無與使用玻尿酸還是空白對照組有顯著相關,另外眼前房閃光的有無與使用玻尿酸還是空白對照組同樣有顯著相關,且在自體血清組還是空白對照組之間亦有相關。綜合以上之結果,乳鐵蛋白、玻尿酸及自體血清眼藥水對於改善眼表臨床症狀、加速角膜上皮癒合及幫助角膜基質膠原纖維重建這三方面無顯著之療效。玻尿酸眼藥水能夠避免嚴重前葡萄膜炎的發生以及讓角膜維持在完整非潰瘍的狀態。自體血清同樣能夠避免嚴重前葡萄膜炎的發生。
Serious corneal ulceration is a potentially vision-threatening condition in small animals. Although serious corneal ulceration may respond to conventional medical managements, a number of patients still require surgical interventions, such as conjunctival graft and biomaterial grafts. However, the surgery may be unavailable in some patients owing to high costs or unsuitable body conditions. Several studies have explored the potential of lactoferrin, hyaluronic acid, and autologous serum eye drops to promote wound healing. The aim of this study was to evaluate and compare the efficacy of the three kinds of eye drops for the treatment of experimentally induced corneal stromal wound in rabbits. A total of 35 New Zealand white rabbits were used as experimental animals and divided into five equal groups corresponded to five different eye drops, including lactoferrin (LF), lactoferrin negative control (LF-N), hyaluronic acid (HA), autologous serum (AS), and phosphate buffered saline (blank control, BC). Initially, three rabbits from each group underwent the acute eye irritation test, and no irritation was found. Next, a unilateral 8-mm diameter and 375-µm depth corneal stromal wound was made in each rabbit, and the eye drops of each group was applied topically four times per day for 28 days. Clinical signs and corneal defect area were recorded at 1, 2, 3, 4, 5, 6, 7, 10, 13, 16, 19, 22, 25, 28 days after wounding, and the corneas were excised for histological examination in the end of the experiment. The result showed no significant difference in the clinical ophthalmic examination scores, the corneal epithelial defect area, and the histologic results among the groups at each point of time. From the perspective of the whole experimental period, there was a significant difference in the absence of corneal ulcer between HA and BC group. Besides, there was also a significant difference in the absence of aqueous flare between HA and BC group, and so was AS and BC group. In summary, the application of lactoferrin, hyaluronic acid, and autologous serum eye drops did not accelerate corneal wound healing and improved the clinical signs, but hyaluronic acid is advantageous to maintain the corneal integrity and avoid anterior uveitis compared to phosphate buffered saline. The use of autologous serum eye drops is also advantageous to avoid anterior uveitis compared to phosphate buffered saline.
文章公開時間: 2019-08-20
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