臺灣博碩士論文加值系統

敗血性休克的特徵為全身性血管阻力降低，而其導致病患死亡的主要原因則為多重器官衰竭所致。其致病機轉可能是發炎調控因子促使自由基、nitric oxide (NO) 過量生成，進而導致全身血液動力學情況惡化與氧氣的供需失衡，最後產生多重器官衰竭和死亡。近年來，活化型1,25-dihydroxy-vitamin D3 (1,25(OH)2D3) 是一個重要的調節鈣、磷衡定。此外，1,25(OH)2D3也應用在自體免疫性疾病或器官移殖的預防或治療。因此，本論文在研究1,25(OH)2D3對腹膜炎敗血症鼠的可能療效。本實驗以盲腸結紮穿刺 (cecal ligation and puncture, CLP) 手術來誘發Wistar 鼠產生腹膜炎敗血症，進而引起多重器官衰竭，借以檢測血流動力參數、血糖、體溫、肝和腎功能以及血清中一氧化氮含量的變化。實驗動物共分為四組，（一）假手術組(sham-operated, SOP)、（二）1,25(OH)2D3給藥組 (SOP + VD)、（三）盲腸結紮穿刺組 (CLP)、（四）盲腸結紮穿刺1,25(OH)2D3治療組(CLP+VD)。在盲腸結紮穿刺手術後的第3小時，由靜脈輸注1,25(OH)2D3 (100ng/kg)，在第18小時犧牲動物取其胸主動脈、肺臟、肝臟、腎臟等器官，以檢測其病理切片、inducible NO synthase蛋白
質表現及超氧游離基。本實驗結果發現：給予1,25(OH)2D3 對敗血症鼠的治療作用包括：（一）改善血管對正腎上腺素的低反應性、肝腎功能和代謝性酸中毒的現象；（二）減少肺內多形嗜中性球的浸潤；及（三）提高CLP鼠的存活率。所以，1,25(OH)2D3改善 CLP 鼠的低血壓、血管低反應性、細胞毒性、和肝腎功能異常的作用可能是透過減少 PMN 在器官內的浸潤，並進而改善其存活率所致；至於其作用機轉仍有待進一步去釐清。

Septic shock is characterized by a decrease in systemic vascular resistance and its main cause of death is due to multiple organ dysfunction syndrome (MODS). The pathogenesis of sepsis is related to the release of inflammatory mediators and the formation of free radicals and nitric oxide (NO), leading to circulatory failure and an imbalance of between systemic oxygen delivery and demand, and finally causing MODS. 1,25-Dihydroxy-vitamin D3 (1,25(OH)2D3), an active form of vitamin D, is an important regulator of the calcium-phosphate homeostasis. The administration of 1,25(OH)2D3 prevents or cures different autoimmune diseases and graft rejection in human. Thus, this thesis was to examine the possible effect of 1,25(OH)2D3 on peritonitis-induced sepsis in the rat. In this study, the septic shock-induced MODS was performed by cecal ligation and puncture (CLP) in Wistar rats. The changes of homodynamics, blood sugar, rectal temperature, hepatic and renal function as well as the plasma NO level were monitored. Animals were divided into four groups：(1) sham-operation (SOP), (2) SOP+1,25(OH)2D3 (S+VD), (3) CLP, (4) CLP+1,25(OH)2D3 (C+VD). At 3 h after CLP, 1,25(OH)2D3 (100ng/kg) was administered to rats by intravenous injection (i.v.) and animals were sacrificed at 18 h. Then, thoracic aortas, lungs, livers, and kidneys were excised to perform the pathological studies, inducible NO synthase expression and superoxide measurement. Our results showed that 1,25-vit D3 (1) attenuated hyporeactivity to NE and reduced GPT, GOT, CRE, BUN, and LDH levels as well as improved metabolic acidosis, (2) decreased lung PMN infiltration, and (3) increased survival rate in rats compared to CLP group. Thus, the beneficial effect of 1,25-vit D3 on hemodynamics, cytotoxicity, and liver and kidney dysfunction could be associated with the attenuation of PMN infiltration. However, the mechanisms need to be further clarified.

目錄 Ⅰ
圖表目錄 Ⅱ
英文縮寫對照一覽表 Ⅴ
中文摘要 Ⅷ
英文摘要 X
第一章 緒言 1
第二章 材料與方法 22
第三章 結果 37
第四章 討論 52
第五章 結論 68
參考文獻 110

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