大量的ROS產生的氧化壓力所造成發炎反應涉及許多人類疾病，包括骨關節炎(OA)，會破壞關節基質，加速炎症及軟骨細胞凋亡的進程。氫氣(molecular hydrogen, H2)被視為是一種新型具有選擇性的抗氧化物質，其在體內的施用安全性高且無明顯的不良反應。然而因H2在常溫常壓下於水中的溶解度低且易以氣體的形式逸散，導致生物利用率低，在發炎組織處不易累積有效的H2治療濃度。在本研究裡，我們將鎂粉包覆於疏水的聚乳酸-甘醇酸 (poly lactic-co-glycolic acid, PLGA)微球載體內，將其以肌肉注射方式注入老鼠的骨關節炎處進行一原位H2的緩釋系統，同時，經由在體液中鎂鈍化/活化的機轉，此微球載體能夠連續地產生H2，並累積有效的治療濃度以清除病灶處所產生的ROS，進而達到抑制發炎反應並可延緩骨關節炎的進程。本實驗分為三部份，在載體研發方面，此微球系統能穩定產生氫氣，同時分析鎂鈍化/活化現象以及其對環境酸鹼值的影響。在細胞實驗方面，我們證實此微球系統能夠抑制以脂多醣(lipopolysaccharides, LPS)誘導的巨噬細胞之發炎情形。在動物實驗上，微球系統降低ROS及發炎表現；並抑制軟骨細胞凋亡，維持軟骨細胞外基質(ECM)的表現量。證實此產氫微球系統能有效減輕組織發炎現象並保護軟骨，以達到治療骨關節炎的效果。

Excess generation of reactive oxygen species is a crucial factor to trigger inflammation, which is involved in many human pathologies, including osteoarthritis. Hydrogen (H2) is known to have anti-inflammatory effects; however, the bioavailability of directly administered H2 gas is typically poor. Herein, a local delivery system that can provide a high therapeutic concentration of gaseous H2 at inflamed tissues is proposed. The delivery system comprises poly(lactic-co-glycolic acid) microparticles that contain magnesium powder (Mg@PLGA MPs). Mg@PLGA MPs that are intra-muscularly injected close to the OA knee in a mouse model can act as an in situ depot that can evolve gaseous H2 continuously, mediated by the cycle of passivation/activation of Mg in body fluids, at a concentration that exceeds its therapeutic threshold. In the first part of study, we examined particle characterization, including H2 release profile, phenomenon of passivation/activation of Mg, and their effects on environmental pH. In the second part of study, the inhibitory effects of Mg@PLGA MPs on LPS-induced RAW264.7 cell inflammation were verified. In the third part, the analytical data that are obtained in the biochemical and histological studies indicate that the proposed Mg@PLGA MPs can effectively mitigate tissue inflammation and prevent cartilage from destruction, arresting the progression of OA changes. The results demonstrated that the system is an effective modality in the treatment of OA.

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