臺灣博碩士論文加值系統

馬兜鈴酸 (aristolochic acid, AA) 在中草藥引起的腎病變中扮演重要的角色。本研究的目的為藉由投予AA引起馬兜鈴酸腎病變 (aristolochic acid nephropathy, AAN)，以評估人參 (ginseng extrat, GE) 及其成份ginsenoside Rb1、Rd及Rg1對AAN的改善效果。
給予純系小鼠C3H/He (6 week-old male) 3.0 μg/mL AA當飲用水，連續56天，之後治療組分別經口投予GE (125、250、500 mg/kg)或純成份ginsenoside (Rb1、Rd、Rg1) 5 mg/kg連續14天，對照組給予等量蒸餾水，Normal組則全程給予蒸餾水。
藉由測定尿蛋白，尿中N-acetyl-beta-D-glucosaminidase (NAG) 與血中blood urea nitrogen (BUN) 及creatinine，以評估小鼠腎功能；腎組織使用PAS染色觀察病理組織改變，並進行免疫螢光染色 (TGF-β，MMP-9，HGF)，以辨識損傷部位之特異性抗原。
實驗結果顯示，投予GE 250 mg/kg，ginsenoside Rb1, Rg1之治療組的尿蛋白、NAG、BUN、SCr及血糖值都有降低；組織學及免疫螢光染色觀察發現腎組織損傷的情形皆有緩解。根據以上結果發現，人參濃縮劑部分，GE 250的療效最好，其次依序為GE 500 及GE 125。人參皂苷部分，有效程度依序為Rg1、Rb1、Rd。

Aristolochic acid (AA) has been demonstrated to play a crucial role in Chinese herbs nephropathy. The purpose of this study was to evaluate the therapeutic effect of ginseng extrat (GE) and its active component, ginsenoside (GS), on AA-induced nephropathy.
AA was dissolved in distilled water (3μg/ml) as drinking water to C3H/He mice (6 week-old male) for 56 days. The treatment groups were administered orally with GE (125, 250, 500 mg/kg) or ginsenosides (Rb1, Rd, Rg1 5 mg/kg) once daily for 14 days. The control group was administered with distilled water. The normal group was only administered with distilled water throughout the experiment.
Urine protein (UP), urine N-acetyl-beta-D-glucosaminidase (NAG), blood urea nitrogen (BUN) and serum creatinine were determined to evaluate renal function. Renal tissues were served to histological examination (PAS stain and immunofluorescence). The antibodies, including TGF-β (transforming growth factor-β), MMP-9 (matrix metalloproteinase-9), HGF (hepatocyte growth factor), were chosen to recognize the specific antigens in injury sites.
Compared with the control group, urine protein, NAG, BUN, serum creatinine and blood glucose were decreased in the GE 250 mg/kg, ginsenoside Rb1 and Rg1 treatment groups. In histological examination, we observed the alleviation in all treatment groups. According to the study, the effect of GE 250 is superior to the other GE-treated groups and ginsenoside Rg1 has the best effect among all the GS-treated groups.

目 錄 I
圖 目 錄 VI
表 目 錄 VIII
縮 寫 表 i
中 文 摘 要 ii
英 文 摘 要 iii
第一章 緒言 1
第二章 文獻回顧 2
第一節 馬兜鈴酸腎病變的由來 2
第二節 馬兜鈴酸之基本特性 2
2.1 用途 2
2.2 含馬兜鈴酸的生藥及使用現況 3
2.3 結構與特性 4
2.4 馬兜鈴酸的代謝 5
2.5 馬兜鈴酸的致癌機轉 7
第三節 馬兜鈴酸腎病變 (Aristolochic acid nephropathy, AAN).. 10
3.1 臨床表徵 10
3.2 病理特徵 10
3.3 鑑別診斷 11
3.4 致病機轉 13
3.5 藥物治療 13
第四節 馬兜鈴酸腎病變的實驗模型 14
4.1 馬兜鈴酸的急性腎毒性 14
4.2 馬兜鈴酸的慢性腎毒性 15
第五節 腎小管間質性纖維化 17
5.1 TGF-β 21
5.2 MMPs 24
5.3 Hepatocyte growth factor (HGF) 27
第六節 人參 30
6.1 生藥學的考察 30
6.2 人參的藥效研究 31
第七節 人參皂苷 (Ginsenoside Rb1, Rd, Rg1) 33
7.1 人參皂苷之結構特性 33
7.2 人參皂苷Rb1的藥效學研究 34
7.3 人參皂苷Rd的藥效學研究 35
7.4 人參皂苷Rg1的藥效學研究 37
第三章 研究目的 38
第四章 材料與方法 39
第一節 人參濃縮劑在AAN之藥效評估 39
1.1實驗動物 39
1.2實驗藥物 39
1.3實驗設計 39
1.4尿液收集 41
1.5動物犧牲法、血液及組織切片製作 41
1.6尿蛋白、NAG含量測定 42
1.7血清中BUN及Creatinine的含量測定 42
1.8血液中血糖值的含量測定 42
1.9 Periodoic Acid Schiff’s (PAS) stain組織染色 43
1.10組織損傷程度的量化 43
1.11免疫螢光染色 (Immunofluorescence) 44
1.12統計方法 44
第二節 Ginsenoside Rb1, Rd, Rg1在AAN之藥效評估 46
2.1實驗動物 46
2.2實驗藥物 46
2.3實驗設計 46
2.4尿液收集 48
2.5動物犧牲法、血液及組織切片製作 48
2.6尿蛋白、NAG含量測定 48
2.7血清中BUN及Creatinine的含量測定 48
2.8血液中血糖值的含量測定 48
2.9 PAS組織染色 48
2.10組織損傷程度的量化 48
2.11免疫螢光染色 48
2.12統計方法 48
第五章 結果 49
第一節 人參濃縮劑對慢性AAN的藥效評估 49
1.1尿蛋白、NAG含量分析 49
1.2血清中BUN分析 52
1.3血清中Creatinine分析 52
1.4血液中血糖分析 52
1.5組織病理PAS染色 54
1.6組織損傷量化分析 54
1.7免疫螢光染色及量化分析 57
第二節Ginsenoside Rb1，Rd，Rg1對慢性AAN的藥效評估 61
2.1尿蛋白、NAG含量分析 61
2.2血清中BUN分析 64
2.3血清中Creatinine分析 64
2.4血液中血糖分析 64
2.5組織病理PAS染色 66
2.6組織損傷量化分析 66
2.7免疫螢光染色及量化分析 69
第六章 討論 73
第七章 結論 77
參考文獻 78

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