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研究生: 楊子墨
Yang, Tzu-Mo
論文名稱: 七氟醚對於小鼠青春期前大腦發育的影響
Effect of sevoflurane on the development of the brain in pre-adolescence mice
指導教授: 郭余民
Kuo, Yu-Min
學位類別: 碩士
Master
系所名稱: 醫學院 - 細胞生物與解剖學研究所
Institute of Cell Biology and Anatomy
論文出版年: 2023
畢業學年度: 111
語文別: 英文
論文頁數: 50
中文關鍵詞: 七氟醚兒童麻醉大腦發育海馬回
外文關鍵詞: sevoflurane, pediatric anesthesia, brain development, HPC
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  • 七氟醚是一種常用於兒科全身麻醉手術的氣體麻醉劑,它具有快速麻醉與快速甦醒的優點,但近年來在動物研究發現,七氟醚對於發育中的大腦具有神經毒性,會使海馬回的突觸可塑性下降與其細胞凋亡,從而使成年後學習與記憶的能力受損。審視過去的實驗發現,大多是使用出生後7天或更年幼的仔鼠進行此類研究。這階段小鼠大腦發育的程度,相當於人類的足月嬰兒,而人類新生兒手術通常會建議延至一歲後進行手術。為了更真實模擬實際臨床狀況,本研究採以出生後19天的小鼠(大腦發育相當於人類的2歲幼兒)作為動物實驗模型,檢測3%七氟醚(兒科手術常用劑量) 是否同樣會對海馬回產生傷害並影響成年後的行為。我的結果發現,7天大的小鼠,吸入3%七氟醚6小時後,確實會導致海馬回中的細胞凋亡;然而,同樣的處理對19天大的小鼠並不會導致海馬回細胞凋亡,但是會造成突觸相關蛋白的表現量顯著減少。長期觀察的結果顯示,不論是7天大或是19天大的小鼠,吸入3%七氟醚6小時,待長大至60天或更大(大腦發育相當於人類的20歲)都會出現長期記憶受損的現象,但是對運動協調能力、焦慮行為的影響並不明顯。總結此研究,3%七氟醚對19天大小鼠(大腦發育相當於人類的2歲)的大腦發育,會有負面影響,但這結果仍需要人類臨床研究來證實。

    Sevoflurane is a commonly used inhalation anesthetic gas in pediatric surgery. It offers the advantages of rapid induction and emergence from anesthesia. However, recent animal studies have found that sevoflurane exhibits neurotoxicity in the developing brain, leading to cell apoptosis and decreased synaptic plasticity in the hippocampus (HPC). This can result in impaired cognitive abilities related to learning and memory in adulthood. Previous experiments often used postnatal day (PND) 7 or younger mice to investigate the effects of inhaling 3% sevoflurane (a commonly used dose in pediatric surgery) on brain development. At this stage, the degree of brain development in mice is comparable to that of full-term human infants. However, most surgical procedures in human newborns are typically recommended to be postponed until after one year of age. Therefore, this study aimed to understand whether inhaling 3% sevoflurane in PND 19 mice (equivalent to human toddlers aged 2 years) would also cause HPC damage and impact later life. The results of the short-term effects showed that prolonged (6 h here) inhalation of 3% sevoflurane in PND 7 mice led to cell apoptosis in the HPC. Similarly, prolonged inhalation of 3% sevoflurane in PND 19 mice did not cause cell apoptosis in the HPC, but significantly reduced the expression of synaptic-related proteins. The long-term effects revealed that both PND 7 and PND 19 mice exposed to 3% sevoflurane exhibited impaired memory function after the mice turned 60 days old or older (equivalent to human aged 20 years). These findings suggested that the use of 3% sevoflurane in PND 19 mice still carries some risks for brain development. However, these results are limited to animal experiments, and there is no conclusive evidence from clinical studies indicating that sevoflurane use in infants leads to neurodevelopmental problems.

    中文摘要 i Abstract ii 致謝 iii Contents iv Figure contents vi Abbreviations vii Introduction 1 Sevoflurane – general properties Animals 1 Sevoflurane – pharmacodynamics and pharmacokinetics 1 Sevoflurane – mechanism of action 2 Sevoflurane hampers neurodevelopment in infants 4 Sevoflurane affects the hippocampus-related memory function 7 Objective, Specific Aims, and Experimental Designs 8 Material and Methods 9 Results 19 Sevoflurane anesthesia induces apoptosis in the HPC of infant, but not pre-adolescent, mice in a duration-dependent manner. 19 Sevoflurane did not induce neuroinflammation in the developing HPC. 19 Sevoflurane anesthesia reduces the expression of synaptic proteins in the HPC of pre-adolescent mice in a duration-dependent manner. 20 Sevoflurane anesthesia experienced during both the infant and pre-adolescent periods induces a long-lasting anxiolysis effect in adult mice. 21 Sevoflurane anesthesia experienced during both the infant and pre-adolescent periods improves the motor performance in rotarod test in adult mice. 23 Sevoflurane anesthesia experienced during both the infant and pre-adolescent periods impairs the HPC-related learning and memory functions in the adult mice. 23 Discussion 26 Conclusion 31 References 32 Table contents 39 Figures 40

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