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研究生(外文):Li-MIin Hsu
論文名稱(外文):Propofol improves autonomic dysfunction and survival time in conscious septic rat model
指導教授(外文):RC Yang
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近年來敗血症的死亡率仍然沒有顯著的改善。敗血性休克的發生是造成敗血症死亡率高的主要原因,佔加護病房死亡原因的10%。加護病房常使用Propofol來鎮靜病人,但 Propofol除了麻醉鎮靜效果外,於細胞實驗中也發現有抗發炎以及清除自由基的角色。本研究以清醒大鼠闌尾結紮穿刺術誘發敗血症模式,觀察Propofol是否對於敗血症具有保護效果。實驗內容包括紀錄敗血症存活時間、敗血性休克血壓變化情形,以非侵入性的心率變異性分析(HRV- LF/HF ratio)作為交感神經調控功能的指標,並以敗血症大鼠腦幹誘發型一氧化氮合成酶(i-NOS)的偵測探討作用機轉。實驗結果發現敗血性休克後血壓在5小時內迅速下降,發生循環功能突然失能(cardiovascular sudden collapse),病程中後期交感神經調控功能會減低,Propofol可經由減緩循環功能突然失能發生的時間,延長存活時間。這效應似乎與腦幹內減低誘發型一氧化氮合成酶合成有關,進而透過保護交感神經調控功能,避免循環功能突然失能,達到延長敗血症存活時間。
Although several clinical trails have been performed, there is not much improvement in septic mortality in recent years. The major cause of septic mortality is septic shock, which also accounts for 10% of mortality in intensive care unit (ICU). In ICU, propofol is often used for sedation. In addition to the effects of anesthesia and sedation, propofol also has anti-inflammation and free radicles scavenger effects in vitro study. The present study aimed to understand whether propofol has any benefit in treatment of sepsis. This is an in vivo study. We adapted awake CLP-induced sepsis rat model without any anesthesia agent. In the study, there were records of sepsis survival time and the change status of blood pressure. In addition, HRV LF/HF ratio (heart ate variability, low frequency/high frequency), a method of non-invasive recording of ANS (autonomic nervous system) was also used. The rat brain stem i-NOS was detected by western blot to explain the mechanism. The results show that cardiovascular sudden collapse happened after the onset of septic shock, and the modulation function of ANS decreased after the late stage of sepsis. Propofol would protect the dysfunction of ANS modulation by reducing the i-NOS production in rat brain stem during sepsis. With above mechanisms, propofol would improve the condition of cardiovascular sudden collapse after septic shock and prolong the survival time of sepsis.
The study showed the basic evidence, that propofol would protect the function of ANS modulation in septic rat model. The results would provide another choice in treating sepsis patients.
Key words: sepsis, septic shock, HRV, propofol
摘要 4
第一章 序論 7
第二章 研究動機與目的 14
第三章 實驗材料與方法 16
第四章 結果 24
第五章 討論 38
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