臺灣博碩士論文加值系統

背景目的:本研究的目的是探討在類固醇誘導的胰島素阻抗（steroid-induced insulin-resistant, SIIR）大鼠，餵食不同中草藥水萃取物後的降血糖效果和機制。一為烏靈參（Xylaria nigripes, XN），其為藥用真菌被廣泛使用在中國傳統醫學中；另一為梔子(Gardenia jasmindides Ellis；GJ)，此藥材的活性成分具有降低血糖、提升胰島素分泌及降低血脂等功效。
材料方法: SIIR大鼠隨機分為實驗組(saline)及對照組(烏靈參500 mg/kg；梔子200 mg/kg)。我們將烏靈參和梔子的水提取物，餵食類固醇誘導的胰島素阻抗（SIIR）大鼠後，監測相關降血糖功效並探討作用機制。
結果: 烏靈參提取物對SIIR大鼠的降血糖作用，可能與血清素和提高SIIR大鼠胰島素的敏感性有關。梔子水提取物則因PPARγ的活化，可改善在SIIR大鼠的胰島素阻抗的降血糖作用。
結論：烏靈參和梔子的水提取物，具有可做為在2型糖尿病與胰島素阻抗時的胰島素增敏劑之新藥開發潛力。

Abstract

Background: The aim of this study was to explore the hypoglycemic effects and mechanisms of the Chinese medicine aqueous extract in steroid-induced insulin-resistant (SIIR) rats. One of Xylaria nigripes (XN) is a medicinal fungus that is broadly used in traditional Chinese medi¬cine, another for Gardenia jasminoides Ellis（GJ）is a medicinal herbs, exhibit a hypoglycemic effect by improving insulin secretion and lowering plasma lipids.
Methods: In the present study, we fed a water extract of XN and GJ to steroid-induced insulin-resistant (SIIR) rats and observed changes in signaling proteins in order to elucidate the mechanisms of the insulin-sensitizing effect of XN and GJ and evaluate its possibility as an insulin-sensitizing agent. SIIR rats were randomly divided into a control group (i.e., saline) and experimental groups (XN 500 and GJ 200 mg/kg).
Results : In summary, the XN extract may have hypoglycemic effects in normal Wistar and SIIR rats that may have a serotonin-related hypoglycemic effect and enhance insulin sensitivity in the SIIR rats. The optimal dose of GJ aqueous extract of 200 mg/kg exerts a PPARγ-activating hypoglycemic effect and improves insulin resistance in SIIR rats.
Conclusions: Therefore, they were a potential an insulin-sensitizing agent in type 2 diabetes mellitus with insulin resistance.

目錄
表目錄 I
圖目錄 II
摘要 III
ABSTRACT IV
第一篇 前言 6
第一章：糖尿病成因 10
第二章：糖尿病分類 13
第三章: 糖尿病的併發症 13
第一節：神經受損（神經病變） 14
第二節：對大血管造成傷害（稱之為大血管疾病） 15
第三節：對小血管造成傷害，如微血管（稱之為小血管疾病） 16
第四章: 第二型糖尿病的侵襲性 19
第一節 糖尿病的病理發生機轉 21
第二節 個體脂肪組織與糖尿病的發生有關 22
第五章 中西醫臨床糖尿病治療與用藥 25
第一節 西醫口服降血糖藥物 25
第二節 傳統中醫藥在臨床的治療 27
第三節 經由其他分生路徑治療探討 28
第六章：研究構想 31
第一節：動機 31
第二節：目的 31
第三節：策略 32
第四節：假說 33
第二篇 烏靈參 34
第一章: 烏靈參命名與來源 35
第一節：藥材介紹 35
第二節：化學組成 36
第三節：生物活性功能文獻探討 38
第二章：實驗設計 42
第三章：研究材料方法 43
第一節：烏靈參藥材萃取過程 43
第二節：檢測烏靈參色胺酸含量 43
第三節：動物模型 45
第四節：實驗動物步驟 45
第五節：採血及血糖檢測的方法 45
第六節：血清胰島素的測定(assay of plasma insulin) 46
第七節：胰島素敏感度之評估（HOMA值） 46
第八節：蛋白質西方轉漬法分析（protein western blotting assay） 47
第九節：血清素阻斷試驗 (serotonin blocking test) 48
第十節：組織免疫染色(assay of immunohistochemistry) 48
第十一節：血中游離脂肪酸測定(assay of the plasma glucose and FFA levels) 49
第十二節：統計分析(statistical analysis) 49
第四章、研究結果-烏靈參 51
第一節：不同動物模型血糖值之比較 52
第二節：烏靈參對不同動物模型血糖之影響 54
第三節：不同動物模型在服用烏靈參水萃物後之胰島素、胰島素阻抗及游離脂肪酸值 57
第四節：胰島素訊息傳遞 59
第五節：腓腸肌組織免疫染色 61
第六節：推測烏靈參在體內可能之降血糖路徑 63
第五章、討論 65
第六章、結論 69
烏靈參小結 70
Summary of XN 71
第三篇 梔子 73
第一章：梔子的命名與來源 73
第二章：梔子有效成分 74
第一節：有效成分分析 74
第二節：現代中藥藥理學 76
第三節：梔子文獻探討 77
第四節：梔子影響血脂之相關研究 80
第三章：實驗設計 82
第四章：研究材料方法 83
第一節：梔子 83
第三節：動物模型 83
第四節：採血及血糖檢測的方法 84
第五節：血清胰島素的測定(assay of plasma insulin) 84
第六節：胰島素敏感度之評估（HOMA值） 84
第七節：蛋白質西方轉漬法分析（protein western blotting assay） 85
第八節：血中游離脂肪酸測定(assay of the plasma glucose and FFA levels) 86
第九節：統計分析(statistical analysis) 87
第五章 結果 88
第一節：梔子的降血糖最佳劑量 88
第二節：梔子在SIIR的降血糖效果 91
第三節：梔子的胰島素增敏效果評估 94
第四節：梔子在SIIR肌肉細胞中的胰島素受體信息傳遞（Western Blot ） 96
第六章 討論 98
梔子小結 100
Summary of GJ 102
第七章 總結 104
參考文獻 107
附錄一、論文發表Papers published（1） 126
附錄二、論文發表Papers published（2） 127

表目錄
表格一、不同動物模型之胰島素、胰島素阻抗指數、游離脂肪酸（FFA）在不同時間點下的平均值(N=6)。 58
表格二、Normal-rat餵食saline及不同濃度的梔子後0、30、60分鐘後的血糖值。 89
表格 三、 梔子應用SIIR大鼠的胰島素敏感度評估 95

圖目錄
圖1、實驗流程圖 42
圖2、烏靈參水抽物在HPLC中分析出之色胺酸 44
圖3、比較動物造模前後血糖值。 53
圖4、烏靈參對不同動物模型血糖之影響 55
圖6、腓腸肌組織免疫染色。 62
圖7、烏靈參在體內可能之降血糖路徑圖。 64
圖9、實驗流程圖 82
圖10、正常大鼠服用不同濃度梔子60分鐘後的降糖百分比。 90
圖11、正常大鼠及類固醇胰島素阻抗大鼠之血糖值比較。 92
圖12、梔子在SIIR的降血糖效果 93
圖13、胰島素訊息蛋白之變化。 97

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