马兜铃酸致大鼠慢性肾小管-间质损伤的初步研究  

Induction of Chronic renal tubuler - interstitial injury in rats by Aristolochic acid

作　　者：张晓明[1] 郑法雷[1] 李艳[1] 段林[1] 金晶[1] 薄玉红[1] 黄庆元[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,北京100330

出　　处：《中国中西医结合肾病杂志》2001年第1期6-9,共4页Chinese Journal of Integrated Traditional and Western Nephrology

摘　　要：目的：目前国内外尚未见有马兜铃酸（ＡＡ）诱导实验动物慢性肾间质纤维化的报告。本研究目的在于初步观察不同剂量的 ＡＡ可否引起大鼠慢性肾小管－间质损伤。方法：实验动物分为 ３组：（１）低剂量 ＡＡ组（ＡＬ组， Ｎ＝２０）：给以ＡＡ ２．５ｍｇ·ｋｇ－１·ｄ－１，腹膜内注射共１２周；（２）高剂量ＡＡ组（ＡＨ组，Ｎ＝２０）：给以ＡＡ ５ｍｇ·ｋｇ－１·ｄ－１，腹膜内注射共 １２周；（３）对照组（Ｃ组，Ｎ＝６）：给以生理盐水腹膜内注射，每只 ２ ｍｌ／ｄ，共 １２周。 ＡＬ、ＡＨ两组在用药后１、２、４、８、１２周分别处死４只大鼠，Ｃ组动物实验结束时处死，分别进行尿蛋白定量，尿β２－ＭＧ、肾功能、肾脏病理等方面的检查。结果：ＡＬ组在用药后１２周血ＢＵＮ水平有明显升高（Ｐ＜０．０５）；ＡＨ组在用药后８、１２周血ＢＵＮ水平均有明显升高（Ｐ＜０．０５、Ｐ＜０．０１）；而两组动物在用药后各时间点均未见尿蛋白、尿β２－ＭＧ、Ｓｃｒ水平明显升高（Ｐ＞０．０５）；肾病理检查可见两组动物８～１２周后有轻度肾小管－间质损害，尤以 ＡＨ组较为明显。结论：木研究中应用的一定剂量和时间的马兜铃酸可诱导大鼠发生慢性肾小管－间质损害及ＢＵＮ升高，但诱导实验动?Objective: It has not been reported that the aristolochic acid (AA) may induce chronic renal interstitial fibrosis in rats. The goal of this study is to examine if AA may induce chronic renal tubules or interstitial injury in rats. Mathods: Female wister rats were divided into three groups. 1. low dosage AA group (AL group, n = 20); AA(2. 5 mg. kg-1 d-1) intraperitoneal injected(ip) for twelve weeks ;2. High dosage AA group (AH group, n = 20) ;AA(5 mg·kg- 1·d- 1 ), ip, for twelve weeks;3. Control group (n = 6);normal saline(2 ml/d), ip, for twelve weeks. In AL and AH groups four rats at 1, 2, 4, 8, 12 week and in control group six rats at 12 week were satisfied. The urine, blood and renal specimen were taken for the 24 hours urine protein quantitative analysis, urine β2 microglobulin(β2- MG), renal function measurement and pathological study. Results: The blood urea nitrogen (BUN)levels were significantly increased at 12 week in AL group (P < 0. 05 ), and at 8, 12 week in AH group (P<0. 05 P<0. 01); But the 24 hours urine protein, β2- MG and serum creatinine (Scr) were onot increased markedly in both AL and AH groups (P > 0. 05 ). The renal pathologic examination showed slight tubule- interstitial injury in AL group and mild to moderate injury in AH group at 8, 12 week. Conclusion: In this study we found that aristolochic acid at 2. 5 - 5 mg·kg- 1·d- 1 may induce chronic renal tubular - interstitial injury and elevation of BUN in rats. Further studies are needed to develop the chronic renal interstitial fibrosis model of this animal.

关 键 词：马兜铃酸 肾小管-间质损伤 马兜铃酸肾病 

分 类 号：R285.5[医药卫生—中药学]