[Establishment of model of aristolochic acid-induced chronic renal interstitial fibrosis in rats].
OBJECTIVE
To study chronic renal interstitial fibrosis induced by aristolochic acid (AA) in animal models.


METHODS
Female Wistar rats were divided into two groups: AA group (n = 42) peritoneally injected with AA (5 mg.kg-1.d-1) for 16 weeks and control group (n = 5) peritoneally injected with normal saline (2 ml/d) for 16 weeks. The body weight of rats was taken. At week 8, 12, 16, and 24 six rats were killed in the AA group. The five rats in the control group were killed at week 24. Specimens of lood and urine were taken before the animals were killed. Specimens of renal tissue were taken after the animals were killed. Twenty-four hour urine protein, urine beta 2 microglobulin (beta 2-MG), and renal function were tested regularly. Pathological examination, including tubulo-interstitial area calculation, was made to the renal specimens.


RESULTS
The body weight of rats in AA group became significantly lower than that of the control rats after 16 weeks' AA injection (P < 0.01). The blood urea nitrogen (BUN) and serum creatinine (Scr) in AA group increased significantly than those of the control group at the 16th, 20th, and 24th weeks (P < 0.05). Optical microscopy showed tubular-interstitial damage in AA group in 16 weeks. Renal tubular atrophy and multifocal renal interstitial fibrosis were shown in 24 weeks. The area of renal tubule increased and the area of the lumen remarkably decreased at week 16 compared with those in the control group. The area of renal tubule decreased remarkably and the area of renal interstitial greatly in the AA group at week 24. Electrical microscopy showed increase of primary and secondary lysosomes and diasappearence of part of brush border of tubular endothelial cells at week 16, and accumulation of secondary lysosome in cytoplasm at weeks 20 and 24 in the AA group. Histoimmunofluorescence showed that IgG, IgA, IgM, C3, and C1q were negative in the renal tissue of experimental animals.


CONCLUSIONS
Animal models with chronic renal tubuloointerstitial nephropathy induced by aristolochic acid were successfully established. Aristolochic acid may have chronic toxicity to renal tissues, and cause chronic renal interstitial fibrosis in rats.
Zheng
F
F
Department of Nephrology, Chinese Academy of Medical Science, Peking Union Hospital, Beijing 100730, China.
Zhang
X
X
Huang
Q
Q
D000818:Animals; D034341:Aristolochic Acids; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D002908:Chronic Disease; D003401:Creatine / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis / Q000097:blood / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000187:drug effects; D009395:Nephritis, Interstitial / Q000097:blood / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D010616:Phenanthrenes / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
D034341:Aristolochic Acids; D002273:Carcinogens; D010616:Phenanthrenes; C000228:aristolochic acid I; D003401:Creatine