蛇床子超临界提取物肝肾毒性及代谢组学的初步研究  

Study on Metabonomics and Hepatic-renal Toxicity of Extractum Fructus Cnidii Made by Supercritical Fluid Extraction

作　　者：韩亮[1] 冯毅凡[2] 江涛[3] 王亮[2] 赵建荣[2] 石忠峰[1] 

机构地区：[1]广东药学院产业办,广州510006 [2]广东药学院中心实验室,广州510006 [3]广东药学院实验动物中心,广州510006

出　　处：《中药新药与临床药理》2012年第2期131-135,共5页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金资助项目(30801543)

摘　　要：目的以常规毒理学指标研究蛇床子超临界提取物的毒性,比较蛇床子组、模型组和空白组的尿液代谢表型差异。方法将SD大鼠随机分为蛇床子组、四氯化碳组和空白组,给药后收集尿液和血液,采用全自动生化仪测定血清中与肝脏、肾脏功能代谢有关的各项指标,用超高效液相色谱-四级杆飞行时间质谱(U-PLC/Q-TOf MS)技术测定大鼠的尿样,利用主成分分析(PCA)对其数据进行处理。结果与空白组比较,蛇床子组中碱性磷酸酶(ALP)活性明显下降,而谷丙转氨酶(GPT)、谷草转氨酶(GOT)、总胆红素(TBI)、血尿素氮(BUN)、血肌酐(CRE)都略有上升。与四氯化碳组比,蛇床子组中GPT、GOT、ALP都存在非常显著性差异。代谢组学分析组间表型差异明显。结论蛇床子超临界提取物具有一定的毒性,在临床使用时应予注意。Objective With the blood biochemical markers as the comparative indexes, the urine metabonomlcs pro file were investigated to study the toxicity of Extractum Fructus Cnidii （EFC） made by supercritical fluid extraction. Methods The rats were randomly divided into EFC group, carbon tetraehloride group and blank control group. The urine and blood were collected after administration. The blood biochemical analysis was carried out by Automatic Chemistry Analyser and the data were statistically processed by T-test. The rat urine was analyzed by UPLC/Q-TOf MS and then subjected to data process and principal component analysis（PCA）. Results The alkaline phosphatase （ALP） activity of EFC group was markedly lower, and the serum levels of glutamate-pyruvate transaminase （GPT）, glutamic oxalacetic transaminase （GOT）, total bilirubin （TBI）, blood urea nitrogen （BUN）, and serum creatinine （CRE） were slightly higher than those of the blank control group. The differences of GPT, GOT and ALP were signif icant between EFC group and carbon tetrachloride group. Metabonomics profile difference was obvious between the three groups. Conclusion Extractum Fructus Cnidii made by supercritical fluid extraction has toxicity and should be used carefully in clinic.

关 键 词：蛇床子 肝毒性 肾毒性 超高效液相色谱-四级杆飞行时间质谱联用 代谢组学 

分 类 号：R285.5[医药卫生—中药学]