苍耳子对大鼠肝脏毒性作用的代谢组学研究  

Metabolomics study on Fructus Xanthii-induced hepatotoxicity in rats

作　　者：曹敏[1] 武斌[1] 马丁[1] 白宇[1] 刘树民[1,2] 

机构地区：[1]黑龙江中医药大学中医药研究院,哈尔滨150040 [2]黑龙江中医药大学北药基(础与应用研究省部共建教育部重点实验室,哈尔滨150040

出　　处：《药物不良反应杂志》2011年第5期287-293,共7页Adverse Drug Reactions Journal

基　　金：国家自然科学基金资助项目(30873435)

摘　　要：目的:观察苍耳子对大鼠尿液代谢轮廓、整体表征和血液生化指标等的影响,探讨代谢组学方法在中药毒性评价中的作用。方法:用随机数字表法将30只雄性Wistar大鼠分为苍耳子低剂量组、高剂量组和对照组,每组10只。苍耳子低剂量和高剂量组大鼠分别经灌胃给予一定容量的含苍耳子水提取液(相当于生药1.05和21.0 g/kg),1次/d,共28 d;对照组给予同体积0.9%氯化钠溶液。给药期间观察大鼠体重、被毛、运动及精神状态的改变;给药前和给药7、14、21、28 d检测血清丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)水平,收集24 h尿液,用超高效液相色谱/飞行时间质谱方法测定大鼠尿液代谢轮廓和整体表征。结果:苍耳子高剂量组大鼠在给药期间陆续出现被毛光泽度下降、脱毛、活动量和摄食量减少、反应迟钝等现象。苍耳子低剂量组仅2只大鼠在给药28 d后表现为少动喜卧,被毛光泽度下降。苍耳子高剂量组大鼠给药21和28 d时体重均明显低于苍耳子低剂量组(P<0.05)和对照组(P<0.01),苍耳子低剂量组与对照组大鼠体重在各时间段的差异均无统计学意义(均P>0.05)。苍耳子高剂量组大鼠给药21 d时的ALT、AST水平[(42.9±3.9)U/L、(107.9±12.7)U/L]明显高于低剂量组[(33.8±4.4)U/L、(95.8±16.6)U/L]和对照组[(31.8±4.4)U/L、(93.5±15.8)U/L],差异均有统计学意义(均P<0.05),给药28 d时苍耳子高剂量组血清ALT、AST水平达峰值。苍耳子低剂量组不同给药时间血清ALT、AST水平与对照组比较差异均无统计学意义(均P>0.05)。苍耳子高剂量组给药第7、14、21、28天24 h尿液代谢物表型的聚类分布均偏离对照组,且随给药时间的延长而增大。苍耳子低剂量组给药第7、14、21天24 h尿液代谢物表型的聚类分布位于对照组附近且与对照组有部分重叠,给药28 d时出现单独聚类。结论:用代谢组学方法检测苍耳子肝毒性灵敏度较高,可用�Objective ： To observe the effects of Fructus Xanthii on urinary metabolic profile and overall characterization and blood biochemical indicators in rats in order to explore the application of metabolomics method in evaluation of toxicity in traditional Chinese medicine. Methods： Thirty male Wistar rats were divided into the low-dose group, the high-dose group, and the control group using random-digital table method, each group comprised 10 rats. The rats in the low-dose and high-dose groups were gavage-fed a certain volume of suspension containing aqueous extract of Fructus Xanthii （ equivalent to crude drug 1.05 and 21.0 g/kg） once daily for 28 days, respectively. The rats in the control group were gavage-fed the same volume of 0.9% sodium chloride solution. The changes in body weight, coat, movement and mental status in rats were observed during the drug administration. The serum levels of ALT and AST were measured before drug administration and 7,14,21, and 28 days after drug administration, respectively. A 24-hour urine sample of each rat was collected and the metabolic profiles and the overall characterization were determined using ultra-high performance liquid chromatography/time of flight mass spectrometry. Results： The rats in the high-dose group developed lusterless fur, depilation, decrease in food ingestion and activities, and uoresponsiveness during the drug administration. Only 2 rats in the low-dose group developed lassitude and lusterless fur 28 days after drug administration. Twenty-one and 28 days after drug administration, the body weight of rats in the high-dose group were markedly lower than that in the low-dose group （P 〈 0.05 ） and the control group （P 〈0. 01 ）, but the differences in body weight between the low-dose group and the control group was not statistically significant in each time point （ all P 〉 0.05 ）. Twenty-one days after drug administration, the levels of ALT and AST in the high-dose group[ （ 42.9±3.9 ） U/L, （ 107.9±12.7）U/L] were markedly

关 键 词：苍耳子 肝毒性 代谢组学 

分 类 号：R285[医药卫生—中药学]