臺灣博碩士論文加值系統

根據世界衛生組織於2010年發表的十大死因，腦中風排名第二，腦中風通常會伴隨著永久性肢體不良。腦中風有許多危險因子包含糖尿病、高血壓、高膽固醇、抽煙、心臟疾病等。研究報導指出糖尿病患者相較於正常人其發生中風的機率較高，故此研究的目標在於討探第二型糖尿病如何影響中風。實驗方法為使用第二型糖尿病小鼠 ( db/db，leptin receptor knockout mice ) ，將其中大腦動脈結紮 ( middle cerebral ischemia occlusion，MCAO ) 並夾住兩側頸動脈15分鐘後再灌注24小時。 實驗結果顯示糖尿病小鼠的體重、血中膽固醇、血糖、三酸甘油脂以及胰島素皆顯著高於db/+ control小鼠。db/db小鼠之死亡率與腦梗塞體積亦顯著性高於db/+ control小鼠，透過神經性評估試驗包括Bederson score、 Grip test、 rotor rod的結果發現db/db小鼠受到缺血性中風影響程度較為嚴重。由以上結果顯示糖尿病會加劇缺血性中風造成的傷害。

According to the World Department of Health WHO published in 2010, stroke ranked second among the ten leading causes of death. Stroke is usually accompanied with permanent disability. The risk factor of stroke including diabetes, hypertension, hypercholesterolemia, smoke and heart disease, etc. It has been demonstrated that patients with diabetes were more prone to experience stroke. In other words, people with diabetes are with higher risks to suffer stroke than people without diabetes. Therefore, the present study was to discover how diabetes can affect ischemia stroke outcomes. The leptin receptor knockout mice ( db/db mice ) was used a model of type II diabetes. Ischemia stroke was induced by MCA ligation and both left and right carotid arteries were occluded for 15 minutes, then mice were allowed reperfusion for 24 hours. The results show that body weight, plasma cholesterol, glucose, triglyceride, and insulin were significantly increased in the db/db diabetic mice compared to db/+ non-diabetic controls. The MCAO-induced mortalilty rate, and cerebral infarction were also significantly increased in the db/db mice compared to db/+ controls. In addition, db/db mice exhibited a worsening neurological functions ( including Bederson score、Grip test and rotor rod ) compared to controls. Our results indicated that diabetes aggravate the damage of ischemic stroke.

目錄
指導教授推薦書........................................
口試委員審定書........................................
授權書.............................................iii
致謝...............................................iv
中文摘要 ……………………………………………………………… vi
英文摘要………………………………………………………………..vii
縮寫表………………………………………………………………….viii
目錄……………………………………………………………………....x
第一章 緒論
1.1 腦中風…………………………………………………….………1
1.2 腦中風的分類………………………………………………….…2
1.3 缺血性中風造成腦部損傷的機轉………………………….……4
1.4 糖尿病 …………………………………..………………….……9
1.5 糖尿病的分類 ……………..……………………………….……9
1.6 糖尿病的併發症與中風的關係……...…………………………11
1.7 高血糖加劇中風傷害的機制……...……………………………14
1.8 瘦體素訊號傳遞..……………………………………….……17
1.9 瘦體素缺陷小鼠(db/db mice)…………………………………..19
第二章 研究目的………………………………………………………22
第三章 研究方法與材料………………………………………………23
3.1 實驗設計………………………………………………………...23
3.2 藥品來源………………………………………………………...24
3.3 實驗動物………………………………………………………...24
3.4 活體動物實驗：腦部缺血再灌注損傷之誘導………………...25
3.5 腦梗塞區域體積計算.……………………………………….....25
3.6 生化值測定……………………………………………………...26
3.7 神經性行為評估..……………………………………………… 27
3.8 西方點墨法……………………………………………………. .31
3.9 統計………………………………………………………...........34
第四章 實驗結果………………………………………………............35
第五章 討論與結論……………………………………………............42
附錄(附圖1).. ……………………………………………….………… 47
附錄(附圖2).. ……………………………………………….………… 48
附錄(附圖3).. ……………………………………………….………… 49
參考文獻………………………………………………………..............68

圖表目次
Fig.1 db/+和db/db小鼠在中大腦動脈缺血再灌注手術前後血糖之差異 (尾靜脈) ………………………………………………………50
Fig.2 db/+ 和db/db小鼠在中大腦動脈缺血再灌注手術前後不同時期血流量的差異………………………………………..……………51
Fig.3 db/+ 和db/db小鼠在中大腦動脈缺血再灌注手術後血中膽固醇、三酸甘油脂和非脂化游離脂肪酸的差異 (心臟採血) …………52
Fig.4 利用Bederson score進行神經性行為評估，比較中大腦動脈缺血再灌注手術後db/+和db/db小鼠神經損傷差異………………53
Fig.5 利用Grip test評估中大腦動脈缺血再灌注手術後db/+和
db/db小鼠神經性行為的差異………………………….…………54
Fig.6 利用Cylinder test，比較中大腦動脈缺血再灌注手術後db/+和db/db小鼠間的差異………………………………………………55
Fig.7 以Rotor rod比較中大腦動脈缺血再灌注手術後db/+和db/db小鼠，四肢協調的能力………………………………………………56
Fig.8 db/+和db/db小鼠在中大腦動脈缺血再灌注手術後大腦水腫的情形………………………………………………………………..57
Fig.9 db/+和db/db小鼠在中大腦動脈缺血再灌注手術後腦梗塞體積的差異……………………………………………………………..58
Fig.10 db/+和db/db小鼠在中大腦動脈缺血再灌注手術後死亡率的差異……………………………………………………..…………..59
Fig.11 db/+和db/db小鼠在中大腦動脈缺血再灌注手術後腦組織STAT3蛋白質的表現量…………………………………..……..60
Fig.12 db/+和db/db小鼠在中大腦動脈缺血再灌注手術後腦組織eNOS、p-eNOS蛋白質的表現量………………………………...61
Fig.13 db/+和db/db小鼠在中大腦動脈缺血再灌注手術後腦組織nNOS蛋白質的表現量……………………………………..……62
Fig.14 db/+和db/db小鼠在中大腦動脈缺血再灌注手術後腦組織iNOS蛋白質的表現量……………………………………………..…..63
Fig.15 db/+和db/db小鼠在中大腦動脈缺血再灌注手術後腦組織nitrotyrosine蛋白質的表現量………………………………..….64
Fig.16 db/+和db/db小鼠在中大腦動脈缺血再灌注手術後腦組織PKC-δ蛋白質的表現量……………………………………..…...65
Fig.17 db/+和db/db小鼠在中大腦動脈缺血再灌注手術後腦組織MnSOD蛋白質的表現量………………………………..………66
Fig.18 db/+和db/db小鼠在中大腦動脈缺血再灌注手術後腦組織Cu/ZnSOD蛋白質的表現量………………………………..…...67

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