腰椎管狹窄症（LSCS）是常見的脊椎退化性疾病，隨著高齡社會來臨，患者數量日益上升，造成的背部、下肢疼痛和神經性跛行嚴重影響日常生活活動，LSCS發病原因很多，其中黃韌帶肥厚(LFH)是主要的致病因素，黃韌帶(LF)外觀呈現黃色，主要由彈性纖維及膠原蛋白組成，位於上下脊椎椎板之間，提供保護和穩定功能。目前雖已有大量文獻針對黃韌帶肥厚進行研究，但確切發病機制仍然未知，先前研究表明，老化與黃韌帶增厚及活性氧物質(ROS)表達有關，另外也指出組織內血管密度高低與年齡大小呈負相關，以上這些觀察結果得知黃韌帶肥厚過程與老化之間關聯極為重要，隨著年齡的上升，黃韌帶傾向於增厚，組織內血管密度減少，推測其將因此處於缺氧環境並發生血管新生，一個關鍵的促血管生成因子為缺氧，透過提高細胞內缺氧誘導因子(HIF-1α)，來增加下游血管內皮生長因子(VEGF-A)及其受體(VEGFR-2)表達，最終導致出芽性血管新生，因此，本研究旨在探討黃韌帶因老化引起的缺氧、出芽性血管新生和活性氧物質之間的關係，首先利用不同年齡患者之黃韌帶組織切片及體外培養不同代數黃韌帶細胞觀察相關蛋白表達，實驗透過FG-4592及過氧化氫(H2O2)進一步模擬缺氧和活性氧物質增生，並通過微流體裝置作為體外3D平台來模擬黃韌帶體內微環境，最終結果表明，黃韌帶傾向於抵抗血管生成透過分泌抗血管新生因子，隨著年齡的上升，在環境刺激下包括缺氧及活性氧物質增生，進而誘發病理性的出芽性血管新生。本研究可以為黃韌帶肥厚提出新的致病機制研究以供治療或預防方法。

A common degenerative disease of the spine called lumbar spinal stenosis (LSCS). Patients number increase year after year with the aging society. The main causative factor in LSCS is ligamentum flavum hypertrophy (LFH) to cause back and lower limb pain and neurological claudication, which seriously affects daily activities. Ligamentum flavum (LF) has a yellow appearance and located between the upper and lower vertebral lamina, mainly composed of elastic and collagen fibers, thereby providing protection and stability. Although numerous studies have been conducted on LFH, the exact pathogenesis remains unclear. Aging has been shown to be associated with LF thickening and reactive oxygen species (ROS) expression in previous studies, indicating that vascular density is negatively correlated with age. These observations indicated there has an extremely important association between aging and LFH. LF tends to thicken and vascular density decreases, speculated it would occur in a hypoxic environment and angiogenesis. Hypoxia increases downstream vascular endothelial growth factor (VEGF-A) and its receptor (VEGFR-2) by increasing intracellular hypoxia-inducible factor (HIF-1α), eventually leading to sprouting angiogenesis. Therefore, this study aimed to investigate the relationship between hypoxia, sprouting angiogenesis and ROS caused by aging in LF. Using different ages of LF tissue from patients and cultured generations of LF cells in vitro to observe related protein expression. Through FG-4592 and hydrogen peroxide (H2O2) simulated hypoxia and ROS proliferation, then used the microfluidic device as an in vitro 3D platform closer to the LF microenvironment. The results showed LF tends to resist angiogenesis by secreting anti-angiogenic factors. Environmental stimuli, including hypoxia and ROS proliferation induced pathological sprouting angiogenesis with increasing age. This study can propose a new pathogenic mechanism and treatment or prevention methods for LFH.

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