Investigation of the "dose-time-response" relationships of rhubarb on carbon tetrachloride-induced liver injury in rats
Investigation of the "dose-time-response" relationships of rhubarb on carbon tetrachloride-induced liver injury in rats
复制标题
大黄对四氯化碳致大鼠肝损伤的“剂量-时间-反应”关系研究
DOI：
10.1016/j.jep.2011.03.053
复制
发表时间：
2011-05-17
影响因子：
5.4
通讯作者：
Xiao, Xiao-he
中科院分区：
文献类型：
--
作者：
Xing, Xiao-yan;Zhao, Yan-ling;Xiao, Xiao-he
研究目的：本研究探讨了大黄对四氯化碳（CCl_4）诱导的大鼠慢性肝损伤的保护作用和毒性作用。第4周末，用大黄40 g kg（-1）（高剂量组）、20 g kg（中剂量组）、10 g kg（低剂量组）灌胃，每日1次，连续3周。在第16周结束时，所有大鼠维持1个月，不进行任何给药。分别于第8、12、16、20周末观察大鼠一般情况、肝脏组织病理学改变、血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、总胆红素（TBIL）和透明质酸（HA）水平。结果：大黄高剂量（40 g kg-1）通过逆转肝损伤大鼠的生化指标和组织病理学改变，对肝损伤大鼠具有明显的保护作用。但随着大黄给药剂量和给药时间的增加，这种保肝作用减弱，甚至转化为毒性作用。结论：长期、大剂量使用大黄应同时考虑其安全性，并定期检测肝功能及变化。本研究为临床合理使用大黄等中草药提供了有益的参考。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
Aim of the study: The present study investigated the liver protection and toxicity of rhubarb against carbon tetrachloride (CCl4)-induced chronic liver injury in rats.Materials and methods: The rats were treated by intraperitoneal injection of 10% CCl4 for 12 weeks. At the end of week 4, rhubarb at doses of 40 g kg(-1) (high-dose group), 20g kg(-1) (medium-dose group) and 10 g kg(-1) (low-dose group) was intragastrically administered to CCl4-treated rats once a day for three weeks. At the end of week 16, all rats were maintained for 1 month without any administration. At the end of weeks 8, 12, 16 and 20, the general status of rats, histopathology of liver, serum alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), total bilirubin (TBIL) and hyaluronic acid (HA) levels were observed, respectively. Combined with clustering analysis and correspondence analysis, the "dose-time-response" relationships of rhubarb on the liver injury rats were synthetically investigated.Results: High dose (40 g kg(-1)) of rhubarb exhibited a significant protective effect on injured liver by reversing the biochemical parameters and histopathological changes. But, this hepatoprotective effect will be weakened, even be transferred to toxicity with increasing the administration dose and time of rhubarb. These results were consistent with the histopathological observation and the determination of serum levels.Conclusions: The safety should be considered simultaneously in the long-term and high dose use of rhubarb, the liver function and change should be regularly detected. This study provided some useful references for the clinical rational use of rhubarb and other herbal medicinal products. (C) 2011 Elsevier Ireland Ltd. All rights reserved.