代谢组学方法研究水飞蓟宾对四氯化碳致小鼠肝损伤的保护作用  

Metabonomic Study of Hepato-protective Effect of Silybin for the Carbon Tetrachloride Induced Liver Injure in Mice

作　　者：黄欣[1] 龚益飞[1] 王毅[1] 瞿海斌[1] 程翼宇[1] 

机构地区：[1]浙江大学药物信息学研究所,杭州310058

出　　处：《高等学校化学学报》2008年第4期714-719,共6页Chemical Journal of Chinese Universities

基　　金：国家'九七三'计划(批准号:2005CB523402);浙江省科技计划重大科技攻关项目(批准号:2005C13026);新世纪优秀人才支持计划(批准号:NCET-06-0515)资助

摘　　要：运用代谢组学方法研究四氯化碳(CCl4)致小鼠肝损及水飞蓟宾肝保护作用的机理.通过气相色谱-质谱(GC-MS)技术分析CCl4及水飞蓟宾作用下的小鼠肝组织匀浆及血浆代谢物谱.使用正交偏最小二乘判别分析法研究正常组与CCl4模型组之间的代谢物谱差异,并通过变量重要性投影(VIP)选取肝组织与血浆中各12种标志性代谢物.使用主成分分析法研究水飞蓟宾预防性及治疗性给药对CCl4肝损的干预效果.通过比较选取的标志性代谢物的含量的差异,探讨了水飞蓟宾对CCl4致小鼠肝损的保护机理.结果表明,CCl4作用后,小鼠机体能量代谢、氨基酸代谢及脂类代谢都受到不同程度的影响.水飞蓟宾能有效地缓解CCl4所造成的体内线粒体功能及氨基酸代谢紊乱.采用代谢组学方法能较全面地反应生物体的生理及代谢状态,并可应用于物质毒性和药效评价研究.A metabonomic study for the carbon tetrachloride（ CCl4 ） induced liver injure and the hepato-protective effect of silybin in mice was described. Gas chromatography-mass spectrometry （GC-MS） technique was used to analyze the mice metabonome both in liver tissue extraction and plasma. Orthogonal partial least square-discriminant analysis（0PLS-DA） was processed to analyze the metabonome difference between the control and CCl4 treated samples. Twelve metabolites were selected both in mice liver tissue and plasma metabonome, respectively, via the parameter of variable importance in the projection （VIP）. Principle component analysis（PCA） was employed to process the data from the preventive and therapeutic treatment of silybin for CCl4 induced hepatotoxicity, and the hepato-protective effect of silybin was investigated through the selected responsor metabolites. The amino acids metabolism, energy metabolism and lipids metabolism were seriously disturbed after CCl4 treatment. Silybin could effectively alleviate the mitochondria dysfunction and the pertur- bation of amino acids metabolism. The results obtained suggest that metabonomic studies could better reflect the whole status of metabolism in bio-systems, and could be treated as a potential powerful approach in toxicological and pharmacological studies.

关 键 词：代谢组学 气相色谱-质谱 变量重要性投影 四氯化碳 水飞蓟宾 肝损伤 

分 类 号：O657.6[理学—分析化学] R965.1[理学—化学]