臺灣博碩士論文加值系統

退化性關節炎(osteoarthritis，也叫做骨關節炎) 成因主要由於緩衝墊的軟骨磨損、腐蝕、退化或鈣化，而使得骨骼末端相互磨擦而造成腫痛，是一種老化的疾病。本研究建立以拉曼光譜為檢測工具之分析系統，初始以動物膝關節軟骨為樣本， 評估拉曼光譜顯微系統的功能應用性，建立因素分析與模擬方法。第二階段以拉曼顯微光譜系統為量測工具，結合自行設計的壓力鬆弛效應量測平台測試軟骨的機械特性，探討各種作用力對於動物膝關節軟骨之影響為研究目標；第三個階段利用豬的退化關節，驗證退化性關節炎的動物模型；最終則進入人體退化性關節炎之離體研究，建立完整的軟硬體資料處理系統與臨床相關性評估。
關節軟骨橫切面的掃瞄分析結果發現，可以把1350 cm-1與462 cm-1兩個鍵結當作日後軟骨研究的Raman marker。研究證實軟骨鬆弛效應（relaxation）測試平台結合拉曼光譜系統，可應用在軟骨的機械特性上。本文首先提出loading和unloading時的關節軟骨材料特性差異比較，未來可以應用於組織工程之軟骨培養品質或軟骨退化病變之分析。豬隻骨關節炎診斷方法之拉曼光譜分析及人類退化膝蓋關節軟骨之拉曼分析研究也同樣證實軟骨病變時之特徵指標，主要為amide III envelope (1300-1350 cm-1) 及Mainly skeletal modes (400-500cm-1)。

Osteoarthritis is a degeneration disease that results from corroded or abraded cartilage which acts as buffering cushion. In this study, we set up an analytic system using Raman Spectrum as measuring tool. First, animal''s articular cartilage was used as test sample, and the material properties were assessed using a microscopic Raman Spectrum. Then, a specially designed compressing relaxation measurement system was adapted to the Raman spectrum apparatus to test mechanical properties of the cartilage. The aim was to study the influence various loading stresses on the knee joint cartilage deformation and Raman spectrum. The degenerated cartilages of pig were used as animal model for osteoarthritis verifications. Finally, in vitro osteoarthritis human study was conducted to test the data analysis procedure and the clinical relavency.
The scanning results of the cross section of articular cartilage suggest that the 1350 cm-1 and 462 cm-1 can be as the Raman markers for cartilage study. We have shown the feasibility of mechanical property study of cartilage using of Raman spectrum-scopy and loading-unloading stress relaxation measurement system. The joint cartilage material properties changed during loading and unloading procedure, and the nonlinear viscoelastic behaviour was observed. The Raman spectrum analysis for the diagnosis of osteoarthritis has been tested in degenerating pig and human cartilages, and the results show that the two characteristic indicators are located in the amide III envelope (1300-1350 cm-1) and skeletal modes (400-500cm-1).

誌 謝 I
中文摘要 II
Abstract III
圖目錄 VI
表目錄 IX
第一章 序論 1
1.1. 前言 1
1.2. 文獻回顧 3
1.2.1. 膝蓋軟骨細微結構模型發展 3
1.2.2. 軟骨力學特性分析發展 6
1.2.3. 拉曼光譜在軟骨組織的應用發展 8
1.3. 研究動機與目的 9
1.3.1. 關節軟骨成分之拉曼光譜分析 10
1.3.2. 關節軟骨機械特性之拉曼光譜分析 11
1.3.3. 退化性關節炎的動物模式（豬）分析 11
1.3.4. 人類退化性關節炎分析 12
第二章 研究原理 13
2.1. 拉曼光譜學 ( Raman spectrum ) 13
2.1.1. 光散射現象 14
2.1.2. 拉曼散射波動模型 16
2.2. 關節軟骨生理學 19
2.2.1. 關節軟骨的組成與結構 21
2.3. 關節軟骨生物力學特性 28
2.3.1. 關節軟骨性學特性理論推導 30
2.4. 集群分析法 ( Cluster Analysis ) 35
2.4.1. 階層式分群法（hierarchical clustering） 36
2.4.2. K-means Algorithm 39
第三章 研究方法 40
3.1. 關節軟骨細微結構之拉曼光譜研究 40
3.1.1. 實驗架構 40
3.1.2. 實驗設備 40
3.1.3. 樣本準備 42
3.1.4. 實驗步驟 42
3.1.5. 光譜訊號處理 45
3.2. 關節軟骨相對於彈性變形之拉曼分析 46
3.2.1. 實驗架構 46
3.2.2. 實驗設備 46
3.2.3. 樣本準備 48
3.2.4. 實驗步驟 49
3.2.5. 光譜訊號及力量訊號處理處理 51
3.3. 豬隻骨關節炎診斷方法之拉曼分析 53
3.3.1. 實驗架構 53
3.3.2. 實驗設備 53
3.3.3. 樣本準備 54
3.3.4. 實驗步驟 55
3.3.5. 光譜訊號處理 57
3.4. 人類退化膝蓋關節軟骨之拉曼分析 59
3.4.1. 實驗架構 59
3.4.2. 實驗設備 59
3.4.3. 樣本準備 60
3.4.4. 實驗步驟 61
3.4.5. 光譜訊號處理 62
第四章 結果與討論 63
4.1. 關節軟骨拉曼訊號相對應的鍵結 63
4.2. 關節軟骨細微結構之拉曼光譜研究 69
4.2.1. 影響關節軟骨拉曼散射光譜因素探討 69
4.2.2. 關節軟骨細微結構之拉曼光譜 75
4.3. 關節軟骨相對於彈性變形之拉曼分析 81
4.3.1. 關節軟骨黏彈特性－loading & unloading 探討 90
4.4. 豬隻骨關節炎診斷方法之拉曼分析 94
4.4.1. 拉曼光譜訊號分析－拉曼標誌（Raman marker） 97
4.4.2. 拉曼光譜訊號分析－目視初步分類正常與非正常的差異 98
4.4.3. 拉曼光譜訊號分析－集群分析 99
4.5. 人類退化膝蓋關節軟骨之拉曼分析 104
第五章 結論 113
參考文獻 116

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