含氧化鈰抗氧化劑的透明質酸水凝膠於退化性關節炎的治療

Abstract

退化性關節炎是種相當常見的疾病，會嚴重的影響患者的活動行為及生活品質。目前對於早期的退化性膝關節炎治療方式為注射透明質酸 (HA) 或服用止痛藥，病情嚴重時必須進行人工關節置換手術。透明質酸注射治療是將透明質酸注射進膝關節腔，可以增加滑液囊中的潤滑液，減少關節互相摩擦，達到減輕病人疼痛、延緩退化症狀惡化的效果，在臨床上廣泛應用多年。但因為注射進入的透明質酸會被關節腔內的透明質酸酶和自由基分解，故治療效果短。病人需要接受多次注射治療，在醫療物資及金錢上都造成了相當的損耗。 在以往的文獻指出氧化鈰奈米顆粒 (CeO2) 具有消除自由基、抗发炎的功能，故本研就運用氧化鈰奈米顆粒結合透明質酸，期望可以预防早期退化性关节炎。 本研究運用金屬鹽水解法在常溫下製備氧化鈰納米顆粒，進行如下分析1.氧化鈰納米顆粒物性分析。2.氧化鈰納米顆粒消除自由基功能分析3.氧化鈰納米顆粒體外測試。4. 試驗檢測氧化鈰納米顆粒對初級培養豬軟骨細胞的預防效果。 本研究結果顯示以金屬鹽水解法成功製備出氧化鈰納米顆粒，其在細胞培養基中粒徑為120 nm左右，具有良好的分散性。氧化鈰納米顆粒濃度在6.7 ng CeO2/1x104細胞具有良好的生物相容性。運用過氧化氫的濃度0.03 mmol/1x104細胞處理初級培養豬軟骨細胞30分鐘後可以建立初期退化性關節炎的損傷模型。當初級培養豬軟骨細胞經過氧化鈰納米顆粒/透明質酸共同培養一天後，進行初期退化性關節炎的損傷模型實驗，發現該處理可以減少過氧化氫對初級培養豬軟骨細胞的損傷。 由研究結果得知氧化鈰納米顆粒/透明質酸對於早期退化性關節炎的预防具有潛在性的臨床運用價值。

Osteoarthritis (OA) is the most common type of joint disease, accompanied by varying degrees of functional limitation, reducing life quality of patients, especially knee osteoarthritis. Hyaluronic acid (HA) joint injections and pain relievers are efficient treatments for early stage osteoarthritis of the knee whereas patients have to knee replacement surgery in the later stages of osteoarthritis. After injected directly into the cavity around the knee joint, HA works by acting like a lubricant and shock absorber in the joints, eases the pain and helps the joints to work properly. However, for the decomposition by hyaluronidase and free radicals in knee joint, HA injection treatment has limited effect time. HA injection shows low benefits to patients suffer from knee and joint osteoarthritis. The cerium oxide nanoparticles (CNPs) has been reported that a long time free radical scavenger. CNPs combined with HA expected that extending HA decomposition time and having positive effect to osteoarthritis therapy. CNPs were synthesis by salt hydrolysis at room temperature. This study has divided four parts: 1. to analyze for physical property of CNPs. 2. To exam the free radicals are removed by CNPs. 3. The in vitro assays of CNPs. 4. To exam the CNPs /HA for early protection of chondrocyte. CNPs had successful synthesized by salt hydrolysis with particle size about 120 nm, showed good dispersibility in culture medium and good antioxidant ability. CNPs are biocompatible under the ratio of 6.7 ng/ 1x104 cells. The OA model can be established by the cell treated with H2O2 for 30 min, which ratio to 1x104 cells is 0.03 mmol. The H2O2 damage effect could be resisted when chondrocyte cultured with CNPs /HA after 1 day. The results suggest that CNPs /HA would be a potential candidate for early stage osteoarthritis treatment.