人參及人參皂苷於純系小鼠之馬兜鈴酸腎炎模型的藥效評估

Effects of ginseng and ginsenosides on aristolochic acid-induced nephropathy in inbred mice

葉欣怡(Hsin-I Yeh)

指導教授 ： 陳世銘

臺北醫學大學/藥學院/藥學研究所/碩士(2007年)

摘要

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。

關鍵字

馬兜鈴酸腎病變 ； 人參 ； 人參皂苷ginsenoside Rb1 ； Rd ； Rg1 ； 乙型轉型生長因子 ； 基質金屬蛋白分解酶肝細胞生長因子

並列摘要

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.

並列關鍵字

Aristolochic acid nephropathy (AAN) ； ginseng ； ginsenoside Rb1 ； Rd ； Rg1 ； TGF-β (transforming growth factor-β) ； MMP-9 (matrix metalloproteinase-9) ； HGF (Hepatocyte Growth Factor)

參考文獻

hypokalemic paralysis: aristolochic acid nephropathy

Identification of aristolochic acid in Chinese herbs.

nephropathy and Chinese herbs nephropathy: Separate

target for gene therapy. Kidney International 1997; 51

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