炮制对大黄化学成分和肝肾毒性的影响及其典型相关分析

Effect of processing on the chemical contents and hepatic and renal toxicity of rhubarb studied by canonical correlation analysis

本文采用典型相关分析方法探讨大黄炮制减毒和化学成分改变间的相关性。通过亚急性毒性试验比较大黄不同炮制品肝肾毒性的差异。蒽醌、鞣质类成分含量采用UV-Vis显色法和高效液相色谱法测定。生大黄最大给药量(76g·kg-1)给小鼠连续灌胃14d,可见肝肾损伤作用,而不同炮制品的毒性相对较小,表明炮制具有减毒作用。化学成分与肝肾功能生化指标的典型相关分析结果表明,大黄中所含大类成分与肝肾毒性的相关性顺序为总结合蒽醌>总鞣质>总游离蒽醌;游离态蒽醌肝肾毒性顺序为芦荟大黄素>大黄素甲醚>大黄酸>大黄素>大黄酚;结合态蒽醌肝肾毒性顺序为结合芦荟大黄素>结合大黄素甲醚>结合大黄酚>结合大黄素>结合大黄酸。实验结果提示炮制可降低大黄肝肾毒性,其机制与结合蒽醌和鞣质类成分的下降有关,其中游离和结合态的芦荟大黄素及大黄素甲醚与毒性相关性最强。肝肾生化功能指标中,血清谷丙转氨酶(ALT)和肌苷(CREA)反映肝肾毒性较敏感,提示可作为临床安全性监测指标。

In this article, canonical correlation analysis was used to explore the relationship between the toxicity-attenuating effect and the variation of chemical contents in rhubarb caused by processing. With quasi-acute toxicity test, the difference of hepatic and renal toxicity to mice with the processed materials of rhubarb was researched. The chemical contents of anthraquinones and tannins in rhubarb were measured by UV-vis spectrophotometry and high performance liquid chromatography. The results showed that there were toxic effects to liver and kidney in mice after repeated intragastric administration of rhubarb and its processed materials for 14 days at a dosage of 76 g·kg^-1. The toxic effect of processed materials was much lower than crude drug. With canonical correlation analysis, the sequence of the hepatic and renal toxicity of chemical contents in rhubarb were found as follows： total anthraquinone glycosides （AQGs） 〉 tannins （Tns） 〉 total anthraquinones （AQs）; aloe-emodin （AE） 〉 physcione （Ph） 〉 rhein （Rn） 〉 emodin （Ed） 〉 chrysophanol （Ch） and AEG 〉 PhG 〉 ChG 〉 EdG 〉 RnG of glycosyl-anthraquinone. It could be concluded that processing would attenuate the toxicity of crude drug of rhubarb. The toxicity-attenuating effect might be correlated to the decline of the contents of both anthraquinone glycosides and tannins, especially the aloe-emodin glycoside and physcione glycoside. The results also suggested that the serum alanine aminotransferase （ALT） and creatine （CREA） would be useful to monitor the hepatic and renal toxicity of rhubarb.