Establishment of the aristolochic acid nephropathy in inbred mice and the effect of Bupleuri Radix on the nephritis

• Main Authors: Yang Wen-Chi, 楊文淇
• Other Authors: Chen Shih-Ming
• Format: Others
• Language: zh-TW
• Published: 2005
• Online Access: http://ndltd.ncl.edu.tw/handle/34463192650084569620

碩士 === 臺北醫學大學 === 藥學系 === 93 === Nephrotoxicity induced by weight-control Chinese medicine was reported frequently in recent years. One of the factors is mistaken the herb that contains aristolochic acid (AA). Aristolochic acid nephropathy (AAN) is a unique type of nephropathy, which was characterized by an extensive interstitial fibrosis with rare cell infiltration and tubular atrophy. We tried to establish a chronic interstitial fibrosis model of AAN in inbred mice and investigated the impact of Bupleuri Radix, prednisolone on AAN. Aristolochic acid (AA) dissolved in distilled water (3μg/ml) were administered orally to C3H/He mice (6 weeks, male) as drinking water ad libitum for 4 weeks, control group were treated with distilled water. In the second experiment, they were administered orally with Bupleuri Radix extract (BR) (150, 300, 450 mg/kg), saikosaponin A, C, D, prednisolone (P), BR 300 mg/kg combine with P once a day for 14 days. The control group was treated with distilled water. Urinary protein, urinary N-acetyl-beta-D-glucosaminidase (NAG), blood urea nitrogen (BUN), blood glucose were determined. Renal tissues were served to histological examination (PAS stain and immunofluorescence staining). The antibodies, including murine F4/80 macrophage, TGF-β (transforming growth factor-β), MMP-9 (matrix metalloproteinase-9) was chosen to recognize the specific antigens, which deposited in injury sites. All animals given AA developed elevation of urinary protein, NAG, BUN, blood glucose. The histological examination was observed the typical AAN: tubular atrophy, interstitial infiltration and fibrosis. In the immunofluorescence stain assay, macrophage, TGF-β, MMP-9 were localized in the renal tissue. After discontinuation of AA, renal function was not improved. The amount of urinary protein, NAG, BUN, blood sugar were decreased in the BR 300 mg/kg, saikosaponin A, D, P, BR combine with P-treated groups compared with the control group. The histological examination was observed the alleviation in all treatment groups. The staining areas of macrophage, MMP-9 in the interstitium were significantly increased, and TGF-β was decreased among all groups. Our result demonstrate the therapeutics effect of the treatment as following: BR combine with P have more prior effect than P, BR 300 mg/kg, saikosaponin D, saikosaponin A. This present study offers a new therapeutic trend of utilizing the crude drug preparation with medicine.