全金螢光共振能量轉移系統進行選擇性探測組織蛋白酶K相關的骨鬆疾病

Probing cathepsin K activity with a selective substrate of all gold Forster resonance energy transfer (AG-FRET) is associated with osteoporosis

洪偉晨(Wei-Chen Hong)

指導教授 ： 王志光

高雄醫學大學/生命科學院/醫藥暨應用化學系碩士班/碩士(2016年)

摘要

關節炎是一種常見的慢性疾病，凡是關節軟骨退化或結締組織發炎，造成關節疼痛而影響關節的正常活動，即可稱為關節炎，正常情況軟骨生長速率與退化速率相等，但當軟骨磨損超過再生速度時，開始發生不可逆之關節軟骨退化，而現今大多數的藥物僅能延緩疾病的惡化，並不能使軟骨恢復再生能力。
骨質疏鬆症是一種全身骨骼疾病，特徵是：骨量減少、骨組織的顯微結構變差，造成骨骼脆弱，骨折危險性增高。目前各大醫院對於骨質疏鬆的檢測方法，大多採用: X光、電腦斷層、骨密度檢查儀和超音波，以上市面上檢測骨質疏鬆的方法昂貴、複雜、費時。而且目前一般的健康檢查的項目並沒有針對骨質疏鬆這一方面的檢查出現，而骨質疏鬆在現今高齡化的社會又是一項常發生的疾病，其影響力不容小覷。
近年來，在學者致力研究下使得關節炎與骨質疏鬆的治療露出曙光，因此如果能即早發現疾病，並且使用抑制破壞骨細胞激素已達到骨細胞未被破壞且可治療及修復的前提下，可使關節的使用期限增長、骨質流失的速率減緩，因此疾病的診斷顯得更為重要。
本研究設計一個全金螢光探針，作為關節炎與骨質疏鬆的偵測。利用螢光共振能量轉移原理，以高生物相容性的奈米金桿作為基材，鍵結一段可被關節炎與骨質疏鬆所釋出酵素組織蛋白酶K剪切的胜肽並修飾上高生物相容性的螢光奈米金團簇，做為偵測這兩種疾病的螢光探針，在生物體外探討偵測關節炎與骨質疏鬆的可能性。

關鍵字

螢光共振能量轉移 ； 組織蛋白酶K ； 關節炎 ； 骨質疏鬆

並列摘要

Arthritis is a common chronic diseases, all of articular cartilage degeneration or inflammation of the connective tissue, causing joint pain and affect the normal activities of the joints, arthritis can be called, normal cartilage degradation rate equal to the growth rate, but when the cartilage wears over playback speed and start an irreversible degeneration of the articular cartilage, and most of today's drugs only slow the disease progression, it does not make cartilage restore regenerative capacity.
Osteoporosis is a systemic skeletal disease characterized by: reduced bone mass, deterioration of bone tissue microstructure, resulting in brittle bones, increased risk of fracture. Currently the major hospitals for detection of osteoporosis, they use: X ray, computed tomography, ultrasound and bone density tester, more than the market to detect osteoporosis is expensive, complex and time-consuming. And general health check of the project and did not check for osteoporosis in this regard appear, and osteoporosis in today's aging society is a frequently occurring disease, its influence can not be underestimated.
In recent years, under such scholars committed to research and treatment of osteoporosis arthritis exposed dawn, so if the next immediate early detection of diseases, and the use of hormones to inhibit the destruction of bone cells have reached the bone cells are not destroyed and to treat and repair of the premise, make joint use of the growth period, slowing the rate of bone loss, the diagnosis of the disease is more important.
In this study, the design of a full gold fluorescent probes as arthritis and osteoporosis detection. Utilizing the principle of fluorescence resonance energy transfer, high biocompatibility of gold nano-rods as the substrate bonding period may be arthritis and osteoporosis cathepsin K enzyme cut and modified peptides released from the high biological compatibility fluorescent nm gold clusters, as the detection of both diseases fluorescent probes in vitro to explore the possibility to detect arthritis and osteoporosis.

並列關鍵字

Forster resonance energy transfer ； cathepsin K ； arthritis ； osteoporosis

參考文獻

1. 黃永彥，骨質疏鬆症，合記出版社，1999。

3. 鄧修國，保密防跌,談骨質疏鬆症

5. Nature Biotechnology, 2001, 19, 316-317.

11. Li, X.; Kao, F. J.; Chuang, C. C. Express, 2010, 18, 11335-11346.

15. Bonnet, C. S.; Walsh, D. A. Rheumatology, 2005, 44, 7–16.