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研究生: 洪小芳
Hung, Hsiao fang
論文名稱: 中草藥抗氧化萃取物對肝臟疾病的 保護機轉及信號傳遞路徑的探討
The protective mechanisms and signaling pathways of antioxidants from herbal extract in liver disease models
指導教授: 鄭啟清
Jeng, Kee-Ching
傅化文
Fu, Hua-Wen
口試委員: 黎耀基
陳春榮
侯建維
學位類別: 博士
Doctor
系所名稱: 生命科學暨醫學院 - 分子與細胞生物研究所
Institute of Molecular and Cellular Biology
論文出版年: 2012
畢業學年度: 100
語文別: 英文
論文頁數: 89
中文關鍵詞: 丁豎杇有絲分裂活化蛋白質激酶第二型環氧化酶
外文關鍵詞: Elephantopus scabe, Teng-Khia-U, COX-2
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  • 丁豎杇 (Elephantopus scaber)常用於治療腎炎、疼痛以及發燒症狀,然而,直接的作用機制並不清楚。此研究在脂多醣體刺激發炎的BV-2微小膠細胞以及急性肝損傷的SD大鼠系統中探討丁豎杇所引發的效應。實驗結果顯示,在BV-2細胞系統中,丁豎杇會使脂多醣體刺激所產生的一氧化氮、介白素-1、介白素-6、活性氧化物以及前列腺素E2產量降低。而且,丁豎杇可明顯降低對於脂多醣體刺激的大鼠其血清中麩丙酮酸轉胺酶和丙氨酸轉胺酶的含量。此外,丁豎杇的水萃取成分(非酒精萃取成分)在BV-2細胞中會抑制脂多醣體誘發的p38以及JNK有絲分裂活化蛋白質激酶並呈現劑量抑制性,而對於第二型環氧化酶則是輕微的抑制作用;然而,在脂多醣體刺激的大鼠,丁豎杇會降低肝臟細胞中的p38和第二型環氧化酶。綜合上述結果,脂多醣體刺激造成急性肝損傷的大鼠中,丁豎杇對其肝臟的保護作用機制與抗氧化效應、抑制p38有絲分裂活化蛋白質激酶與第二型環氧化酶有關。


    Elephantopus scaber Linn. (ES, Teng-Khia-U) has been traditionally used for the treatment of nephritis, pain, and fever; however, the direct evidence is lacked. The effects of ES on lipopolysaccharide (LPS) induced inflammation of BV-2 microglial cells and acute liver injury in Sprague-Dawley (SD) rats were investigated in my study. The results showed that ES reduced LPS-induced nitric oxide (NO), interleukin (IL)-1, IL-6, reactive oxygen species (ROS), and prostaglandin (PGE2) production in BV-2 cells. ES significantly decreased serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in LPS-treated rats. Furthermore, the water extract, but not the ethanol extract, of ES dose-dependently inhibited LPS-induced p38, JNK mitogen-activated protein kinases (MAPK), and slightly inhibited cyclooxygenase-2 (COX-2) in BV-2 cells, but decreased p38 MAPK and COX-2 expressions in the liver of LPS-treated rats. Taken together, these results indicate that the protective mechanism of ES involves an antioxidant effect and inhibition of p38 MAP kinase and COX-2 expressions in LPS-stressed acute hepatic injury in SD rats.

    Abstract i 中文摘要 ii Abbreviations iii Contents v Chapter 1 General Introduction 1 1.1 AN OVERVIEW OF THE CHINESE HERB ELEPHANTOPUS SCABER LINN. 2 1.1.1. The Constituents of Elephantopus scaber Linn. 3 1.1.2. The effects of Elephantopus scaber Linn. 4 1.2 AN OVERVIEW OF THE LIVER DISEASE 5 1.2.1. Acute and chronic liver diseases 6 1.2.2. The biochemical diagnosis of liver injury 9 1.2.3. Role of cytokines in the pathophysiology of liver injury 10 1.2.4. Reactive oxygen and reactive nitrogen species of liver injury 11 1.2.5. Prostaglandins and cyclooxygenase in liver injury 13 1.2.6. Signaling pathway of inflammatory events in liver injury 15 1.2.7. Role of the Kupffer Cells in liver injury induced by LPS 18 1.3 OBJECTIVE OF THIS WORK 19 Chapter 2 The Protective Effect and Signaling Pathway of The Chinese Herb Elephantopus scaber in Rat Liver Injury Model 21 2.1 INTRODUCTION 22 2.2 MATERIALS AND METHODS 24 2.3 RESULTS 29 2.4 DISCUSSION 31 2.5 FIGURES 34 Chapter 3 Conclusion 45 References 47 Appendix I 丁豎杇 56 Appendix II Manuscript of The Accepted Paper 59 Biography 88

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