2015-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/647993長期透析對末期腎臟病患者是維持生命必須的治療。然而，因腹膜結構及功能的 改變而使長期腹膜透析受限。這個獨特的病理現象是增厚的腹膜，由密集膠原纖維沉 積組成。腹膜纖維化會導致失超過濾失效，無法繼續腹膜透析，甚至引起嚴重的包膜 性腹膜硬化症。 腹膜纖維化主要最後的表現會在腹膜組織中有不適當的間質堆積。我們認為間質 鍵結是過多的細胞外間質堆積的主要原因，並且造成腹膜纖維化。離胺基酸氧化腺是 膠原蛋白及彈力蛋白互相鍵結的起始酵素，會促使細胞外間質蛋白質鍵結。在不同的 組織及細胞中，低氧狀態，高糖，細胞激素已知會促進離胺基酸氧化腺產生。因為腹 膜透析需要使用非生理性的透析液，造成許多的生長因子及發炎細胞激素上升。因此， 我們假設離胺基酸氧化腺在透析液中，因為高糖的狀態或是發炎的細胞激素而增加其 表現，造成細胞外間質鍵結、堆積，而促進腹膜纖維化。 在這個研究，我們將探討離胺基酸氧化腺在腹膜纖維化之角色。我們將探討離胺 基酸氧化腺在人類腹膜腔間皮細胞及纖維母細胞調控之分子機制。最後，我們會設計 體外腹膜等同系統來檢視是否高糖會促進離胺基酸氧化腺的活性，並造成腹膜滲透性 不當的上升。Chronic dialysis is a life-sustaining treatment for patients with end stage renal disease. However, long-term PD is limited because of structural and functional alternation of the peritoneal membrane. The unique pathological finding is thickened submesothelial zone, which composed with dense collagen deposition. The peritoneal fibrosis would lead to ultrafiltration failure, technique failure, and even catastrophic encapsulating peritoneal sclerosis. The main and common final presentation of peritoneal fibrosis is an inappropriate accumulation of matrix within peritoneal tissue. We propose extracellular matrix cross-link is critical to its excess deposit and contributes to peritoneal fibrosis. Lysyl oxidase (LOX) is a copper- and lysyl-tyrosyl cofactor containing amine oxidase that has been known to play a critical role in the catalysis of crosslinks in extracellular matrix proteins.In various tissue and cells, lysyl oxidase is upregulated by hypoxia status, high glucose and cytokines, including transforming growth factorp , platelet-derived growth factor, and fibroblast growth factor. However, the effect of LOX in peritoneal fibrosis has not been delineated. Since unphysiological dialysate, often with high glucose, is used in peritoneal dialysis, and is associated with many growth factors and inflammatory cytokines and PF, we hypothesize LOX is upregulated in the peritoneal fluid due to high glucose dialysate or inflammatory cytokines and then leads to extracellular matrix cross-link and promotes peritoneal fibrosis. In the present study, we aim to explore the role of lysyl oxidase in peritoneal function and fibrosis. We plan to explore the molecular mechanism of regulation of lysyl oxidase in human primary mesothelial cells and peritoneal fibroblasts. Then, we aim at designing an in vitro peritoneal equivalent via organotypic cultures and examine whether high glucose-induced changes in LOX activity may contribute to surplus permeability.離胺基酸氧化腺腹膜透析葡萄糖腹膜纖維化細胞激素lysyl oxidaseperitoneal dialysisglucoseperitoneal fibrosiscytokine