臺灣博碩士論文加值系統

敗血症、敗血性休克及其伴隨併發之多重器官衰竭是加護病房主要的死亡原因。本篇研究主要探討臨床上所使用的抗發炎藥物對於敗血症肺損傷之合理性。先前的實驗顯示，隨著敗血症的進展其肺泡巨噬細胞的凋亡隨之增加且伴隨肺巨噬細胞數目的減少。為了解臨床上使用解熱鎮痛及抗發炎藥物可能加重肺泡細胞的傷害及引起免疫機轉之改變，因此本研究我們使用與臨床敗血症相關盲腸結紮穿刺手術模式引發大白鼠敗血症，於手術結束後止痛期 (3小時) 或高血液動力時期 (9小時)分別給予溶劑或抗發炎藥物COX-1抑制顯著藥物indomethacin、COX-2抑制顯著藥物ibuprofen、專一性COX-2抑制劑NS-398及類固醇藥物dexamethasone的治療。在晚期敗血症二十小時偵測其肺泡巨噬細胞凋亡比例及肺清除細菌的防禦能力。
我們以支氣管灌流技術將肺泡巨噬細胞分離，其純度約大於95%，以流氏細胞儀雙染方式分析，發現手術後3小時給予COX-2顯著抑制藥物ibuprofen及專一性COX-2抑制劑NS-398具有明顯惡化加重肺泡巨噬細胞凋亡作用，同時伴隨肺部清除細菌能力下降。在手術後3小時給予COX-1顯著抑制藥物indomethacin則具有保護肺泡巨噬細胞的抗凋亡作用，然而類固醇類的抗發炎藥物卻對於肺泡巨噬細胞的凋亡及肺清除細菌的能力無明顯影響。
以上研究顯示COX-1顯著抑制藥物具有保護肺泡巨噬細胞凋亡作用，但專一性COX-2抑制劑會增加肺泡巨噬細胞凋亡比例且伴隨肺清除能力減少進一步惡化敗血症的肺損傷。本研究顯示，敗血症動物的肺傷害會因COX-2抑制劑的使用而加重，因此在敗血症選擇COX-1而非COX-2抑制性抗發炎的藥物對於減輕肺傷害是合理的。

Acute lung injury (ALI) is a major complication of sepsis, which could leads to the increased susceptibility to pulmonary infection.
Nonsteroid anti-inflammatory drugs (NSAIDs) are commonly used clinically for the management of sepsis-related manifestations, including pain, fever, and inflammation. However, their effects on septic lung injury are not recognized. Recent studies revealed that NSAIDs cause apoptosis in several cell types. Our hypothesis was that, during the process of sepsis, the usage of NSAIDs may enhance AM apoptosis and, thereafter, decrease the ability of the lung to clear bacteria. In this study, SD rats were cecal ligated and punctured (CLP). At 3 and 9 h after CLP, septic rats were treated with traditional NSAIDs (indomrthacin or ibuprofen) or COX-2-seclective blockers (NS-398). The rats were scarified at 20 h and the lungs and AM were obtained to investigate bacterial burden and apoptosis, respectively.
The results showed a deteriorated AM apoptosis and a parallel increased lung bacterial burden in the COX-2-selective blocker-treated septic animals, but not in the early traditional COX-1-predominant NSAIDs (indomethacin) treated ones.
Consequently, the utilization of NSAIDs, especially COX-2-seclective blockers, should be careful or limited in septic subjects to prevent further damages and secondary infections of septic lungs.

目錄
中 文 摘 要
英 文 摘 要
致 謝 目錄
表 目 錄
圖 目 錄
專 有 名 詞 符 號 與 縮 寫
第 一 章 緖 論
第 一 節 敗 血 症 之 簡 介
第 二 節 敗 血 症 引 發 肺 器 官 的 損 傷
第 三 節 抗 發 炎 藥 物 使 用 於 敗 血 症 治 療 抑 制 發 炎
主 要 物 質 的 產 生
第 四 節 研究設計與目的
實 驗 設 計 及 方 法
第一節 給藥方式
第二節 誘發敗血症大白鼠動物模型
第三節 分離肺泡巨噬細胞及其相關實驗
第四節 細胞形態與細胞計數
第五節 肺部巨噬細胞凋亡之偵測
第六節 肺部細菌培養
第七節 統計方法
第 三章 結果
一、誘發敗血症大白鼠之外觀
二、手術解剖上差異
三、肺泡巨噬細胞形態和比例目
四、支氣管灌流之肺泡巨噬細胞數
五、肺泡巨噬細胞細胞凋亡之比例
六、肺部細菌培養的結果
第 四 章 討 論
第 五 章 結 論
第 六 章 參 考 文 獻

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