消癌解毒方干预W256移植瘤大鼠的血浆代谢组学分析  

Plasma Metabonomics Analysis in Rats of W256 Sarcocarcinoma Treated by Xiaoai Jiedu Prescription

作　　者：杨静[1,2] 陈海彬[1] 周红光[1] 吴勉华[1] 

机构地区：[1]南京中医药大学第一临床医学院,南京210046 [2]徐州市中医院,江苏徐州221003

出　　处：《中国实验方剂学杂志》2015年第23期77-82,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81102563);国家教育部高等学校博士学科点专项科研基金项目(20113237110001)

摘　　要：目的:采用代谢组学方法检测W256移植瘤大鼠血浆内源性代谢物异常变化及消癌解毒方对移植瘤大鼠代谢紊乱的调节作用,寻找移植瘤生长可能的生物标志物,探索消癌解毒方代谢性作用机制。方法:采用Wistar大鼠腹腔接种Walker-256瘤株制作腹水瘤模型,移植至大鼠腋下,成移植瘤模型;大鼠分为消癌解毒方低、中、高剂量组和模型组、空白组,收集给药后的第1,6,11天的血浆,采用GC-MS联用仪对血浆中内源性分子进行测定,采用偏最小二乘法判别分析对多变量数据进行分析并建立模型,结合数据库进行代谢物鉴定,进行t检验组间比较,并分析关联代谢通路变化。结果:与空白组相比,模型组大鼠在第11天时,有30个化合物发生了显著变化,给予消癌解毒方后,有10种内源性物质得到了不同程度的转归。结论:血浆中有30种内源性物质与W256肉瘤的生长密切相关,消癌解毒方可使造模后大鼠血浆中异常变化的化合物水平有不同程度的恢复,这10种化合物可能是该复方作用靶点,其发挥药效作用可能与调节相关代谢途径有关。Objective： To investigate abnormal changes of plasma endogenous metabolic in rats with W256 sarcocarcinoma and regulation of Xiaoai Jiedu prescription（ XJP） on metabolic disorder of transplanted tumor rats. To explore mechanisms of XJP on anti-tumor based on metabonomics. Method： W256-transplanted tumor rats model were established and were divided into the control group,the model group and XJR treatment groups.Plasma smaples were collected on the 1^st,6^th and 11^th day after administration. Endogenous metabolites of all groups were determined by GC-MS. Partial least squares-discriminant analysis（ PLS-DA） was applied to analyze multivariate data and established model, metabolite identification was adopted database, t test was used in significant statistical analysis and metabolic pathways. Result： Compared with the control group,rats in the model group on the 11^th day,30 endogenous metabolites significantly changed,10 endogenous metabolites got differently restoration to the normal group after treated XJR. Conclusion： Thirty endogenous metabolites may be potential metabolic biomarkers. Abnormal metabolite levels in plasma can be partly recovered by XJR,these 10 endogenous metabolites may be biomarker of XJP working. And potential antitumor effects of XJR may be contributed to regulation of related metabolic pathways.

关 键 词：消癌解毒方 W256移植瘤 代谢组学 作用机制 色氨酸 鸟氨酸 

分 类 号：R945[医药卫生—微生物与生化药学] R969.1[医药卫生—药剂学]