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研究生:江欣蓓
研究生(外文):Shin-Bei Chiang
論文名稱:第二型糖尿病小鼠之胃黏膜神經
論文名稱(外文):Gastric Mucosa Innervation in Type 2 Diabetic Mice
指導教授:謝松蒼謝松蒼引用關係
口試委員:孫家棟趙啟超曾屏輝
口試日期:2015-06-22
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:解剖學暨細胞生物學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2015
畢業學年度:103
語文別:中文
論文頁數:34
中文關鍵詞:非胰島素依賴型糖尿病自主神經病變胃腸道併發症胰島素糖尿病小鼠胃黏膜神經密度
外文關鍵詞:Noninsulin-dependent diabetes mellitusautomatic neuropathygastrointestinal complicationsinsulindb/db micemucosal nerve fiber density (MNFD)
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近年來,隨著飲食西化、生活型態的改變與肥胖之盛行,全球糖尿病的發生率與盛行率正快速的逐年上升,而有先前研究指出,大約90%的糖尿病患者屬於非胰島素依賴型的第二型糖尿病 (Noninsulin-dependent diabetes mellitus)。糖尿病患者自主神經病變 (autonomic neuropathy)會影響患者之胃腸道系統,進而引起胃腸道併發症 (gastrointestinal complications),包括胃輕癱 (gastroparesis)、腹瀉 (diarrhea)、便祕 (constipation)等等不適的症狀,常會影響患者之生活品質。先前研究指出,糖尿病患者胃蠕動異常造成之不適症狀除了自主神經病變之外,血糖控制不佳可能也參與其中。
有研究指出胃黏膜取樣 (gastric mucosal biopsy)可用以診斷胃自主神經病變,然而探討第二型糖尿病與胃黏膜神經表現之相關研究相當少,也沒有任何研究探討經胰島素或藥物治療後,胃黏膜神經表現是否會有變化,因此,本實驗使用第二型糖尿病小鼠模式 (db/db mice)探討其胃黏膜神經之表現,並且探討糖尿病小鼠經過胰島素或藥物治療後,胃黏膜神經表現之變化,此外,我們亦會探討血糖與胃黏膜神經表現之間的相關性。
我們的實驗結果顯示,週齡八週與十二週糖尿病小鼠 (db/db mice)之體重與血糖均比對照組小鼠 (m/m mice)高,且胃黏膜神經密度 (gastric mucosa nerve fiber density, MNFD)之表現比對照組小鼠低。經過胰島素或liraglutide治療四週後,糖尿病小鼠依然維持較高的體重與血糖,而胃黏膜神經密度之表現相較於未治療之糖尿病小鼠並無明顯變化。最後,我們探討血糖與胃黏膜神經密度之間的相關性,發現高血糖與胃黏膜神經密度有負相關。本研究說明了第二型糖尿病小鼠之胃黏膜神經表現異常,且高血糖影響其中之表現,未來需更進一步探討長期血糖控制與胃黏膜神經表現之間的相互關係,並且找出胃黏膜神經的表現與胃腸道併發症之間的因果關係。


In the recent years, diabetes mellitus is one of the most common metabolic disorders, and the number of diabetic patients has been increasing worldwide. Previous studies have indicated that approximately 90% of patients with diabetes are diagnosed with type II diabetes (noninsulin-dependent diabetes mellitus). Autonomic neuropathy affecting the gastrointestinal system in diabetes mellitus is frequently associated with gastrointestinal symptoms, including gastroparesis, diarrhea, constipation, and so on. This uncomfortable symptoms often affect the quality of life of patients. Previous research suggested that abnormal blood glucose control, in addition to autonomic neuropathy, contribute to the pathogenesis of disordered gastric motility
Clinically, gastric mucosal biopsy is a safe and practical method for histologic diagnosis of gastric autonomic neuropathy. However, there is a lack of gastric mucosa study in type 2 diabetes and the effects of medicament treatments (insulin / liraglutide) in type 2 diabetes were not yet explored. Therefore, we use a model of type 2 diabetic mice (db/db mice) to investigate the manifestations of gastric mucosal nerve fiber. In addition, we explored the correlation among blood glucose and gastric mucosal nerve fiber.
Our results showed that the body weight and blood glucose of the db/db mice were much higher than the control mice (m/m mice) at the age of the 8 and 12 week. However, the gastric mucosa nerve fiber density (MNFD) of the db/db mice were lower than that of the control mice. After insulin and liraglutide treatment for 4 week, the db/db mice still maintain the higher body weight and blood glucose. There was no change in MNFD between db/db mice and mice receiving treatments. We explored the correlation between blood glucose and gastric mucosa nerve density. This research suggests that the gastric mucosal innervations was reduced in the type 2 diabetic mice. In the future, we will further explore the relationship between the long-term blood glucose control and gastric mucosa innervation.


致謝---- i
中文摘要-------- ii
ABSTRACT------- iii
目錄---- v
圖目錄-- vi
Chapter 1------ 引言---- 1
Chapter 2------ 方法---- 4
2.1---- 動物---- 4
2.1.1-- 實驗動物 4
2.1.2-- Insulin與Liraglutide治療 4
2.2---- 體重與血糖測量--- 4
2.3---- 組織取樣 4
2.4---- 免疫螢光染色---- 5
2.5---- 免疫組織化學染色- 5
2.6---- 胃黏膜神經定量--- 6
2.7---- 統計分析 6
Chapter 3------ 結果---- 7
3.1---- 八週小鼠之體重與血糖----- 7
3.2---- 小鼠之胃黏膜區域- 7
3.3---- 八週小鼠之胃黏膜神經密度-- 7
3.4---- 十二週小鼠之體重與血糖---- 8
3.5---- 十二週小鼠之胃黏膜神經密度 8
3.6---- 血糖與胃黏膜神經密度的相關性------- 9
Chapter 4------ 討論---- 10
參考文獻 13
圖表與說明------- 22


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