| Summary: | 碩士 === 臺北醫學大學 === 藥學系 === 94 === Abstract
Many cases about aristolochic acid nephropathy (AAN) have been identified in recent years. The reason is that people mistaken the herb that contains aristolochic acid (AA). AAN is a unique type of nephropathy, which was characterized by extensive cell infiltration, tubular atrophy, and interstitial fibrosis. We established a chronic interstitial fibrosis model of AAN in inbred mice and investigated the efficacy of green tea (GT), (+)-catechin (CAT), pravastatin (P) on AAN.
AA was dissolved in distilled water (3μg/ml) and as drinking water ad libitum to C3H/He mice (6 weeks, male) for 56 days, the control group was administered to distilled water. In the second experiment, they were administered orally with GT (75, 150, 300 mg/kg), CAT (25, 50, 100 mg/kg), P, CAT 50 mg/kg combined with pravastatin (CAT+P) once daily for 14 days. The control group was administered to distilled water.
Urinary protein (UP), 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), TNF-α (tumor necrosis factor-α) were chosen to recognize the specific antigens, which deposited in injury sites.
All animals treated with AA developed increased in UP, NAG, BUN, and blood glucose. In the histological examination, we observed tubular atrophy, interstitial infiltration and fibrosis in the typical AAN. In the immunofluorescence stain assay, macrophage, TGF-β, MMP-9, and TNF-α were localized in the renal tissue. After discontinuation of AA, renal function did not improve.
The amount of urinary protein, NAG, BUN, and blood sugar were decreased in the GT 150 mg/kg, CAT 50 mg/kg , P, CAT+P-treated groups compared with the control group (except for the UP of GT 150 mg/kg ). In the histological examination, we observed the alleviation in all treatment groups. The staining intensity of macrophage, TGF-β, TNF-α were decreased in all groups, and MMP-9 in the interstitium was significantly increased. Our results demonstrate the therapeutics efficacy of the treatment as follow: P > CAT+P > CAT 50 mg/kg. The groups of pravastatin, CAT 50 mg/kg combine with pravastatin have similar therapeutics efficacy. The conclusion of our study is that both pravastatin alone use and pravastatin combined with CAT 50 mg/kg can improve the renal function of AAN patients.
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