慢性马兜铃酸肾病动物模型的建立及其意义  

Establishment of model of aristolochic acid-induced chronic renal interstitial fibrosis in rats

作　　者：郑法雷[1] 张晓明[1] 黄庆元[1] 李艳[1] 段林[1] 

机构地区：[1]中国医学科学院中国协和医科大学北京协和医院肾内科,100730

出　　处：《中华医学杂志》2001年第18期1095-1100,共6页National Medical Journal of China

基　　金：卫生部科学研究基金资助项目 (98 1 0 2 7)

摘　　要：目的　探讨建立马兜铃酸引起的大鼠慢性肾间质纤维化动物模型。方法　将雌性Wistar大鼠分为马兜铃酸组与对照组。马兜铃酸组大鼠腹膜内注射马兜铃酸 5mg·kg-1·d-1共 16周 ,开始用药后 8、12、16、2 0、2 4周分别处死 6只大鼠。对照组大鼠 (5只 )腹膜内注射生理盐水 2ml/d ,共16周 ,2 4周时处死。两组动物处死时分别留取血、尿、肾组织标本 ,分别作生化、病理 (光镜 ,免疫荧光 ,电镜 )等方面的检查及应用电脑软件测定肾小管 间质面积。结果　马兜铃酸组大鼠用药后 16、2 0、2 4周体重明显低于对照组 ;用药后 16周血尿素氮、血清肌酐明显高于对照组 ,2 4周时肾功能损伤进一步加重。光镜检查可见马兜铃酸组大鼠有明显肾小管 间质损伤 ,16周时肾小管面积明显增加 ,管腔面积明显小于对照组 ;2 4周时出现明显肾小管萎缩 ,肾小管面积明显缩小 ,而肾间质面积明显增加 ,肾间质呈多灶性纤维化。电镜检查 16周时肾小管上皮细胞胞质内初级溶酶体、次级溶酶体明显增加 ,部分肾小管上皮细胞刷状缘消失 ;2 0、2 4周时可见胞质内次级溶酶体和髓样小体堆积。结论建立了慢性马兜铃酸肾病动物模型。马兜铃酸具有慢性肾毒性作用 。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 β 2 microglobulin (β 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. Conclusion Animal models with chronic renal tubuloointerstitial nephrop

关 键 词：马兜铃酸 间质性肾炎 疾病模型 实验研究 马兜铃酸肾病 

分 类 号：R-332[医药卫生]