臺灣博碩士論文加值系統

背景：TM-1為aporphine生物鹼類的衍生物，是thaliporphine的新衍生物。之前本實驗室研究發現，單次靜脈注射TM-1在麻醉大鼠和兔子的開胸缺血再灌流實驗具有心臟保護作用。本篇實驗主要研究長期口服TM-1對於心臟冠狀動脈阻塞後再灌流所造成的損傷，是否具有保護的作用，並探討其可能的機轉。

方法：正常ICR小鼠於禁食後口服給予TM-1 20mg//kg，觀察小鼠血糖和胰島素變化。正常、高油飲食引發的第二型、STZ引發的第一型糖尿病ICR小鼠口服兩週的TM-1之後，觀察其水、食物攝取量及體重變化。取其心臟使用Langendorff離體心臟灌流模式，讓全心臟缺血30分鐘，之後再灌流2小時。觀察缺血再灌流後，冠狀動脈血流、心跳速率、心臟梗塞面積以及灌流液中LDH、NO含量的變化。並利用西方點墨法及NOS inhibitor，更進一步探討TM-1的作用機轉。給予離體小鼠心臟組織isoproterenol，觀察心臟收縮力變化。

結果：實驗結果發現正常小鼠口服TM-1之後，可明顯減緩血糖升高，並且能促進胰島素的分泌。另一方面，發現正常及糖尿病小鼠長期口服TM-1之後，不會影響老鼠的食物、水攝取量及體重。心臟經離體缺血再灌流後，發現TM-1能減少正常、第二型、第一型糖尿病老鼠心肌的梗塞面積，並且能讓正常老鼠心臟的LDH釋放量減少。於離體小鼠心房及心室實驗，發現TM-1不會影響其對isoproterenol的反應。此外，長期口服TM-1能阻止缺血再灌流後心臟eNOS表現量減少，在心臟缺血再灌流前給予NOS inhibitor L-NAME，發現老鼠心肌的梗塞面積和LDH釋放量有增加的趨勢。

結論：TM-1對於心臟冠狀動脈缺血再灌流損傷具有保護作用，可能的機轉是透過維持心臟eNOS表現量達到心臟保護作用，減少心肌細胞壞死途徑，來降低心臟再灌流損傷。

口試委員審定書……………………………………… I
誌謝…………………………………………………… II
縮寫表………………………………………………… III
中文摘要……………………………………………… V
英文摘要……………………………………………… VII
第一章 緒論……………………………………… 1
Tab.1-1………………………………………………… 1
Fig.1-1………………………………………………… 3
Fig.1-2………………………………………………… 5
Fig.1-3………………………………………………… 6
Fig.1-4………………………………………………… 7
Fig.1-5………………………………………………… 8
Fig.1-6………………………………………………… 9
Fig.1-7………………………………………………… 10
Fig.1-8………………………………………………… 11
Fig.1-9………………………………………………… 13
Fig.1-10…………………………………………………14
文獻回顧…………………………………………………14
動機及研究目的…………………………………………15
Fig.1-11…………………………………………………16
第二章 實驗材料與方法………………………………17
Fig.2-1………………………………………………… 21
第三章 實驗結果…………………………………… 29
Tab.3-1………………………………………………… 35
Fig.3-1………………………………………………… 36
Fig.3-2………………………………………………… 37
Fig.3-3………………………………………………… 38
Fig.3-4………………………………………………… 40
Fig.3-5………………………………………………… 42
Fig.3-6………………………………………………… 44
Fig.3-7………………………………………………… 46
Fig.3-8………………………………………………… 47
Fig.3-9………………………………………………… 48
第四章 討論………………………………………… 50
Fig.4-1………………………………………………… 56
Tab.4-2………………………………………………… 57
第五章 結論………………………………………… 58
參考文獻……………………………………………… 59

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