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請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/32219
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dc.contributor.advisor賴凌平
dc.contributor.authorYi-Ren Hungen
dc.contributor.author洪一仁zh_TW
dc.date.accessioned2021-06-13T03:37:20Z-
dc.date.available2006-08-02
dc.date.copyright2006-08-02
dc.date.issued2006
dc.date.submitted2006-07-26
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行政院衛生署(2006)中華民國九十三年台灣地區死因統計結果摘要。
dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/32219-
dc.description.abstract背景:組織缺氧後再灌流而引起的損傷,在臨床上是很常見的,除了影響做心血管手術或器官移植病人的預後外,也是中風、心肌梗塞及冠狀動脈阻塞等病人所需克服的難關。二十世紀中期以來,有許多文獻顯示低溫在各種疾病中的應用價值,低溫對於組織缺氧後再灌流損傷的影響,在腦神經已經有多方研究顯示其保護的作用,而在其他重要器官所造成的影響還不是很清楚。本篇實驗主要在研究低溫循環對於心臟冠狀動脈阻塞後再灌流所造成的損傷,是否有其保護的作用,並探討其可能的機轉。
方法與結果:心臟取自成年雄性、重約250-350公克的Wistar大鼠,實驗使用Langendorff離體心臟灌流,將冠狀動脈壓力固定在80mmHg,待流速穩定後給予30分鐘的左主冠狀動脈結紮,之後再灌流2小時。實驗依再灌流的溫度分成三組,37℃為常溫組、34℃和30℃為低溫組,從triphenyl tetrazolium chloride(TTC)染色的結果發現,心肌梗死面積占心臟缺氧區域的比率,37℃一組為66.96 ± 3.29 % (n=12),34℃一組為55.69 ± 3.02 % (n=11),30℃一組為44.56 ± 2.84 % (n=10),低溫組顯著的減少心肌梗死面積。利用西方點墨法觀察各組心臟和細胞凋亡相關的蛋白質表現量,低溫組caspase-3的活化和Bax表現量都減少了,Akt磷酸化的量增加了,且30℃一組都比34℃一組影響來的顯著,而對於Bcl-2、Akt的表現量則沒有影響。
結論:低溫循環對於心臟冠狀動脈阻塞再灌流損傷具保護作用,可能的機轉是經由促進Akt的磷酸化、減少caspase-3的活化和Bax的表現量,進而抑制細胞凋亡途徑,來減少心臟再灌流損傷引起的心肌梗死。
zh_TW
dc.description.abstractBackground: Reperfusion injury has wide clinical relevance. It influences the outcome of patients after cardiovascular and transplant surgery and, even if surgery is not performed, it influences the recovery of patients after stroke, myocardial infarction and coronary occlusion. Hypothermia has been shown to be beneficial in many diseases since middle of the 20th century. Although many researches have demonstrated that hypothermia is protective for brain and neuron after reperfusion, its effects on other important organs are unclear. The aim of the present study was to investigate the effects of hypothermia on coronary occlusion-reperfusion induced myocardial injury.
Methods and Results: We used mature male Wistar rat weighing 250-300g for the experiments. The hearts were subjected to Langendorff-perfusion with 80 mmHg coronary perfusion pressure. Occlusion of the left coronary artery for 30 min followed by reperfusion
For 2 hours was performed. Experiments were divided into normothermic (NT; 37℃) and hypothermic (HT; 34℃ and 30℃) groups. Results of triphenyl tetrazolium chloride (TTC) staining showed that the percentage area of infarction was significantly decreased in the HT group (37℃= 66.96 ± 3.29%, n=12; 34℃= 55.69 ± 3.02 % , n=11; 30℃= 44.56 ± 2.84 %, n=10). Western blot analysis revealed that activated caspase-3, Bax amount were reduced and Akt phosphorylation was enhanced in HT groups. Furthermore, HT 30℃ group had more significant changes than HT 34℃ group. Bcl-2 and total Akt expression showed no significant differences among the three groups.
Conclusions: Inhibition of apoptosis pathway may be one of the mechanisms for the protective effects of hypothermia on coronary occlusion-reperfusion induced myocardial infraction. Inhibition of apoptosis is related to Akt phosphorylation, reduction of Bax expression and inhibition of caspase-3 activation.
en
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Previous issue date: 2006
en
dc.description.tableofcontents縮寫表……………………………………………………… 1
中文摘要…………………………………………………… 2
英文摘要…………………………………………………… 4
第一章 緒論…………………………………………….... 6  
表1-1: 中華民國93年十大死因…………………………….. 7
圖1-1: 缺血再灌流會引起的一連串反應…………………… 9
圖1-2: ROS主要的來源以及其後續的反應…………........... 11
圖1-3: 細胞凋亡兩個主要的途徑…………………………… 13
圖1-4: Bcl-2家族成員……………………………………….. 15
表1-2: caspase家族的成員…………………………………… 16
圖1-5: caspase下游的目標物………………………………… 18
第二章 實驗材料與方法………………………………... 22
第三章 實驗結果………………………………………... 28
圖3-1:低溫再灌流能減少心臟缺血區域的心肌梗死範圍… 29
表3-1低溫再灌流對心跳速率、心律不整及灌流流速的影響.. 31
圖3-2:低溫再灌流能抑制active caspase-3的表現量..... 32
圖3-3:低溫再灌流抑制Bax的表現量…………………….... 34
圖3-4:低溫再灌流對Bcl-2無顯著影響…………………….. 35
圖3-5:低溫再灌流增加phospho-Akt的表限量..............37
圖3-6:低溫再灌流對Akt表現量無影響……………………... 38
第四章 討論……………………………………………... 39
圖4-1:Bcl-2和Bax競爭BH2-only蛋白,抑制Bax活化....... 44
圖4-2:Bcl-2和Bax之間的交互作用………………………….. 44
圖4-3:PI3K-Akt可以抑制心臟再灌流損傷所造成的細胞凋亡 46
第五章 結論與展望……………………………………... 48
參考文獻…………………………………………………... 50
dc.language.isozh-TW
dc.subject細胞凋亡zh_TW
dc.subject冠狀動脈阻塞zh_TW
dc.subject缺氧-再灌流zh_TW
dc.subjectCoronary occlusionen
dc.subjectIschemia-reperfusion: Apoptosisen
dc.title低溫循環可以減少冠狀動脈阻塞再灌流引起之心肌傷害zh_TW
dc.titleProtective Effects of Hypothermia on Coronary Occlusion-Reperfusion Induced Myocardial Injuryen
dc.typeThesis
dc.date.schoolyear94-2
dc.description.degree碩士
dc.contributor.oralexamcommittee蘇銘嘉,江福田,林俊立
dc.subject.keyword冠狀動脈阻塞,缺氧-再灌流,細胞凋亡,zh_TW
dc.subject.keywordCoronary occlusion,Ischemia-reperfusion: Apoptosis,en
dc.relation.page56
dc.rights.note有償授權
dc.date.accepted2006-07-27
dc.contributor.author-college醫學院zh_TW
dc.contributor.author-dept藥理學研究所zh_TW
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