人參及人參皂苷;Rg1 合併去氫羥化腎上腺皮素在純系小鼠之馬兜鈴
酸腎炎模型之藥效評估
Effect of ginseng, ginsenoside Rg1 and prednisolone on aristolochic acid induced nephropathy in inbred mice
中文摘要
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 研究為藉由投予 AA 引起馬兜鈴酸腎病變 (aristolochic acid nephropathy, AAN) 後評估人參濃縮劑 (ginseng extrat, GE) 及其成分人參皂苷 Rg1 (ginsenoside, GS) ，並分別與去氫羥化腎上腺皮質素 (Prednisolone, P) 合併對 AAN 的改善效 果。純系小鼠 C3H/He (6 week-old male) 給予 3.0 μg/mL AA 作為飲用水連續 56 天，之後治療組連續 14 天經口分別投予 GE 250 mg/kg、GS 5 mg/kg、prednisolone 2 mg/kg 及 prednisolone 合併 GE 或 GS；對照組在前 56 天同樣予以 AA 作為飲 用水，在投予治療藥物期間則給予等量蒸餾水；Normal 組則是在整個實驗過程 皆給予蒸餾水。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，以 GE，P，GE+P 及 GS+P 對尿蛋白、
NAG、BUN 及 SCr 值皆能有效降低；組織學觀察各組腎組織損傷的情形皆有緩 解現象；免疫螢光染色觀察發現 TGF-β沈積情形降低，MMP-9 及 HGF 的沈積 增加。根據上述結果得知以合併治療組在各實驗中皆有較佳療效，推測應是 GE 及 GS 結構類似 prednisolone 具有抗發炎效果，可以減少基質堆積並延緩纖維化 過程以降低腎臟損傷程度，且與 prednisolone 合併使用可有加成療效。
英文摘要
Aristolochic acid (AA) has been demonstrated to play an important
role in aristolochic acid nephropathy (AAN). The purpose of this study was to evaluate the therapeutic effect of ginseng extract (GE) or its active component ginsenoside Rg1 (GS), combined with prednisolone on AAN.
AA was dissolved in distilled water as drinking water to C3H/HE mice (6 week-old male) for 56 days. The treatment groups in phase one were administered with GE 250mg/kg, prednisolone 2mg/kg, and both GE and prednisolone orally for 14 days. In phase two, under the same process, GE was replaced by GS. The control group was administered with distilled water and the normal group was only administered with distilled water throughout the experiment. Urine protein, 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 and serum creatinine were decreased at different level in all treatment groups. In the histological examination, we observed the alleviation in all treatment groups. The fluorescence dots of TGF-β were significantly decreased and MMP-9, HGF were significantly increased in experimental groups. Based on our result, both GE and GS combined with prednisolone has the superior effect among the concomitance groups.
Our findings demonstrated that GE and GS are structure analogs of prednisolone and they have anti-inflammatory properties to slow down the fibrosis process and repair the renal injury.
