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研究生:林雅瑩
研究生(外文):Ya-Ying Lin
論文名稱:Hydralazine在腹膜炎引發敗血性休克伴隨多重器官衰竭大鼠之療效
論文名稱(外文):Therapeutic Effects of Hydralazine on Peritonitis-Induced Septic Shock with Multiple Organ Dysfunction Syndrome in Rats
指導教授:吳錦楨
指導教授(外文):Chin-Chen Wu
口試委員:三軍總醫院 廖文進主任、康寧醫護暨管理專科學校 陳秀珍主任、台北榮民總醫院 曹正明主治醫師、中國醫藥大學 黃家樂主任
口試委員(外文):Wen-Jinn Liaw,Shiu-Jeu Chen,Cheng-Ming Tsao,Kar-Lok Wong
口試日期:2011-06-22
學位類別:碩士
校院名稱:國防醫學院
系所名稱:藥理學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2011
畢業學年度:99
語文別:中文
論文頁數:129
中文關鍵詞:敗血症經盲腸結紮穿刺術多重器官結衰竭
外文關鍵詞:SepsisCLPHydralazie
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敗血症往往因控制不當而伴隨有多重器官衰竭,而多重器官衰竭是造成敗血性休克重症病患死亡的重要因素。多重器官衰竭的產生往往導因於全身性的組織之血流灌流不足導致缺氧所致。Hydralazine 具有擴張小動脈,並增加腎血流量;此外,許多證據顯示hydralazine 為強效的自由基清除劑。因此,本實驗以盲腸結紮穿刺手術 (cecal ligation and puncture, CLP)來誘導大鼠產生腹膜炎敗血症,並評估低劑量的hydralazine在敗血症合併多重器官衰竭的大鼠模式下之可能療效。實驗動物分成四組:(1)假手術組(SOP);(2) SOP給藥組 (手術後第三個小時靜脈給予3 mg/kg hydralazine);(3) CLP組;和(4) CLP給藥組(手術後第三個小時靜脈給予3 mg/kg hydralazine)。觀察 18 個小時的血液動力學、血糖、血氧分析、體溫(肛溫)、細胞損傷程度、肝臟及腎臟功能的變化。此外,亦測量血中NO和IL-6及組織中超氧游離基的生成,並於手術後18小時犧牲動物,取出肺臟、肝臟、腎臟及大腸組織進行病理切片分析,而且記錄每個組別的存活率。實驗結果顯示:在腹膜炎誘導敗血症的動物模式下,hydralazine 可以增加組織血流;減少血漿中的NO和IL-6以及組織中超氧游離基的生成;減少多型核嗜中性白血球在肝臟、腎臟和大腸的浸潤;並改善循環衰竭和多重器官功能。因此,降低腹膜炎敗血症的致死率。
Sepsis and its sequelae, multiple organ dysfunction syndrome (MODS), are major contributors of mortality in critical ill. Global tissue hypoxia results from an imbalance between systemic oxygen delivery and demand, and is a key development preceding multiple organ failure and death. Hydralazine preferentially dilates the arterioles and increases renal blood flow. In addition, hydralazine per se has powerful free radical scavenger properties. Therefore, this study was to examine the effect of hydralazine on peritonitis- induced sepsis with MODS in Wistar rats. Intraperitoneal sepsis was induced by a cecal ligation and puncture (CLP) surgery. Animals were divided into four groups: (1) sham operation (SOP), (2) SOP + hydralazine (3 mg/kg i.v. at 3 hr after surgery), (3) CLP, and (4) CLP + hydralazine (3 mg/kg i.v. at 3 hr after CLP). The changes of hemodynamics, blood glucose, blood gas, rectal temperature, lactate dehydrogenase (LDH), hepatic (ALT) function, renal (BUN and CRE) function were monitored over 18 hr. In addition, plasma nitric oxide (NO), interleukin-6 (IL-6) and organs superoxide (O2•−) production were also measured. In addition, lung, liver, kidney and colon were harvested at 18 hr after surgery to perform histo-pathological studies. The survival rate in each group was also calculated. Results demonstrate that beneficial effects of hydralazine on the circulatory failure and MODS caused by peritonitis-induced sepsis were attributed to amelioration of organ blood flow and reduction of plasma NO and IL-6 as well as organ O2•− levels, and decrease of liver, kidney, colon PMN infiltration, leading to decrease of mortality rate in peritonitis-sepsis animals.
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 IX
第一章 緒言 1
第二章 材料與方法 23
第三章 結果 38
第四章 討論 55
第五章 結論 76
參考文獻 120


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