2011-08-012024-05-18https://scholars.lib.ntu.edu.tw/handle/123456789/701556摘要：腰椎椎間盤退化是下背痛的原因之一。椎間盤退化是多種因素所造成的現象，包含了機械性 的因子和生化性的因子。目前雖然有些方法可以減輕痛苦，但效果仍具有爭議性及個體差異。本 計劃將比較電流、電磁場、超音波、高壓氧、和小核酸干擾素等不同處理人類退化性椎間盤細胞， 分析基因、核酸、蛋白質訊息傳導和細胞的變化，希望可以找出抑制細胞凋亡、抑制介白質、及 基質金屬蛋白腺的分泌，並增加聚醣蛋白、第二型膠原蛋白分泌的方法。電磁場可以促進硬骨的 生長和關節軟骨的修復，但對椎間盤細胞並不清楚。超音波促進退化性椎間盤細胞的發炎、再吸 收，但正面的幫助並不清楚。我們最近在JOR 2010發表的結果證明，高壓氧可以增加退化性椎 間盤細胞多醣類，和第二型膠原蛋白的分泌，並壓制iNOs表現和P38MAPK的磷酸化現象，但 電流、電磁場、超音波、高壓氧各種處理之間的交互影響並不清楚。我們將利用微矩陣分析不同 處理方法在同一個檢體造成的基因表現差異，避免個體差異，並利用Q-PCR來確認資料的正確性。 我們也將利用phosphor-kinase array來分析訊號傳遞的路徑，並利用小核酸干擾素來確認。最後我 們將利用Kroeber’s椎間盤退化的動物模型來評估不同處理造成的結果差異性，並利用MRI、免疫 組織染色檢測聚醣蛋白、第二型膠原蛋白、介白質、基質金屬蛋白腺、ADAMTS5，及Safranin O staining等來評估椎間盤軟骨修復的情形，TUNEL staining來評估軟骨凋亡的情形。<br> Abstract: There is evidence that some diet factor play a role in the pathogenesis of Alzheimer’sdisease (AD). Low serum folic acid levels are strongly associated with cerebral cortex atrophy,and also increase risk in the developing of AD. In our pervious study, the APP transgenicmice (Tg2576) received memantine and folic acid showed significant group effects on spatiallearning, and neuronal protection as compared to both memantine treatment only andnon-treatment transgenic controls. In further analysis of global gene expression withmicroarray, folic acid supplement plus memantine group showed a generalized up-regulationof brain gene transcriptions involving in neurogenesis, neuron development ordifferentiation-associated transcription factors, memory and neurotransmitter receptors ascompared to memantine-treated group. In our another animal experiment revealed that folicacid deprivation differentially depleted brain folic acid levels, and increased lipidperoxidation and mtDNA4834 deletions, particularly, in the hippocampus. Upon Aβ challenge,the folate-supplment diet protects various brain regions against lipid peroxidation,mitochondrial genotoxicity and neural death associated with folic acid deprivation. In a pilotstudy designed as APP transfected cell line with folic acid only or with memantine, we foundthat folic acid alone has the same or even better effect to relieve the apoptotic and necroticeffect, and even gene regulation induced by Aβ.3xTg-AD mice are generated from simultaneously microinjecting two transgenes (i.e.,APPSWE and TauP301L) into single-cell embryos from homozygous PS1M146v knock-in mice.They develops two age-related neuropathological features associated with AD, amyloidplaques and neurofibrillary tangle formation, as well as age-related behavioral deficits thatcorrelate with the neuropathology. Using this new model, we want to clarify the exactinfluence of folic acid supplement to the production or degradation of Aβ andhyperphosphorylated tau, neuronal survival, and up-regulation expression of certain geneswhich we found before in the nervous system, and their inter-relationship in degenerativeprocess of Alzheimer’s disease. It is an investigation to study the novel mechanism of folicacid, except one-carbon metabolism, in the nervous system. In addition, amyloid PET is anew-developed tool for quantitative analysis of amyloid loading in vivo, and will be alsoutilized in this study to evaluate the therapeutic effect.椎間盤退化電流刺激電磁場超音波高壓氧Alzheimer’s diseaseFolic acid3xTg-ADAmyloid PET