广防己与粉防己的代谢组学及肝肾毒性的比较研究

[Comparative study on metabonomics and on liver and kidney toxicity of Aristolochia fangchi and Stephania tetrandra].

作者信息

Liang Qi, Ni Cheng, Yan Xianzhong, Xie Ming, Zhang Yanxia, Zhang Qi, Yang Meijuan, Peng Shuangqing, Zhang Yuzhong

机构信息

Department of Formulaology, Beijing University of Chinese Medicine, Beijing 100029, China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2010 Nov;35(21):2882-8.

PMID:21322952

Abstract

OBJECTIVE

Combined the blood biochemical markers, the renal histopathological changes and the metabonomics profile were investigated to study the toxicity differences between Aristolochia fangchi and Stephania tetrandra.

METHOD

Ten rats were randomly selected from 70 male Wistar rats as blank control group. The remaining 60 rats were divided into three groups. The two treated groups were orally administrated by 8.1 g x kg(-1) of A. fangchi and S. tetrandra respectively and the control group by equal volume of distilled water for 4weeks. Before the administrated and every 2 weeks, urine and plasma were collected and their 1H-NMR spectra were acquired, and then subjected to data process and PCA. Blood biochemical analysis and histopathological examination were carried out.

RESULT

On the 2nd weekend, the BUN of the two treated groups, the AST of A. fangchi group were all markedly higher than that of the control group (P < 0.05). Compared with the A. fangchi group, the SCr higher in the S. tetrandra group (P < 0.05). The kidney pathological changes were apparently in the two treated groups and the pathological changes in the liver apparently in the S. tetrandra group. Along with the lasting of administration to the 4th week, the BUN, ALT and AST of the two treated groups, the SCr of A. fangchi group were all significantly higher than that of the control group (P < 0.01). The renal and liver injuries in the two treated groups were all become more seriously. Comparing the A. fangchi group, the BUN, SCr and AST were all higher in the S. tetrandra group (P < 0.05). Compared with control group, the urinary concentrations of citrate, 2-oxo-glutarate, taurine, hippurate, TMAO, creatine and the plasma concentrations of 3-D-hydroxybutyrate, acetone, NAC, OAC, creatinine were all changed.

CONCLUSION

The A. fangchi and S. tetrandra all can induce the renal and liver lesion and its seriousness is correspondent to the lasting of administration. The liver and kidney toxicity of S. tetrandra are all more serious than the A. fangchi.

摘要

目的

结合血液生化指标、肾脏组织病理学变化和代谢组学图谱，研究广防己和粉防己的毒性差异。

方法

从70只雄性Wistar大鼠中随机选取10只作为空白对照组。将其余60只大鼠分为三组。两个处理组分别以8.1 g·kg⁻¹的剂量灌胃给予广防己和粉防己，对照组给予等体积蒸馏水，持续4周。给药前及每2周收集尿液和血浆，采集其¹H-NMR谱，然后进行数据处理和主成分分析（PCA）。进行血液生化分析和组织病理学检查。

结果

在第2周末，两个处理组的血尿素氮（BUN）、广防己组的谷草转氨酶（AST）均显著高于对照组（P < 0.05）。与广防己组相比，粉防己组的血清肌酐（SCr）更高（P < 0.05）。两个处理组的肾脏均出现明显病理变化，粉防己组肝脏出现明显病理变化。随着给药持续至第4周，两个处理组的BUN、谷丙转氨酶（ALT）和AST、广防己组的SCr均显著高于对照组（P < 0.01）。两个处理组的肾脏和肝脏损伤均加重。与广防己组相比，粉防己组的BUN、SCr和AST均更高（P < 0.05）。与对照组相比，尿液中柠檬酸、2-氧代戊二酸、牛磺酸、马尿酸、氧化三甲胺、肌酸的浓度以及血浆中3-羟基丁酸、丙酮、N-乙酰半胱氨酸（NAC）、草酰乙酸（OAC）、肌酐的浓度均发生变化。