基于代谢组学的壮骨关节丸致特异质肝损伤相关易感生物标志物筛查  

Related biomarker screening of Zhuanggu Guanjie Pill induced idiosyncrasy liver injury based on metabolomics

作　　者：唐进法[1,2] 李伟霞 王晓艳[1] 李宇辉[1] 张海珠[3] 曹英杰 牛明[2] 柏兆方 王伽伯[2] 肖小河[2] 李学林[1] TANG Jin-fa;LI Wei-xia;WANG Xiao-yan;LI Yu-hui;ZHANG Hai-zhu;CAO Ying-jiel;NIU Ming;BAI Zhao-fang;WANG Jia-bo;XIAO Xiao-he;LI Xue-lin(Department of Pharmacy,The First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450000,China;China Military Institute of Chinese Medicine,302 Military Hospital of China,Beijing 100039,China;Department of Pharmacy and Chemistry,Dali University,Dali 671000,China)

机构地区：[1]河南中医药大学第一附属医院药学部,郑州450000 [2]中国人民解放军第三○二医院全军中医药研究所,北京100039 [3]大理大学药学与化学学院,大理671000

出　　处：《中华中医药杂志》2018年第10期4336-4340,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金重点项目(No.81630100);国家"重大新药创制"科技重大专项课题(No.2015ZX09501-004-001-008)~~

摘　　要：目的:从代谢组学层面探索壮骨关节丸致特异质肝损伤的物质基础。方法:采用尾静脉注射脂多糖(LPS)法建立免疫应激大鼠模型,以LPS模型大鼠灌胃给药壮骨关节丸(ZGP+LPS)后大鼠血清肝功能丙氨酸氨基转移酶(ALT)活力值与LPS模型组大鼠ALT活力值比较的高低作为是否为易感动物的分组指标(ZGP+LPS给药组≤1倍LPS模型组分为不易感组即肝未损伤组,ZGP+LPS给药组>2倍LPS模型组分为强易感组即肝损伤组,其余为弱易感组)。采用UPLC-QTOF/MS技术,将ZGP+LPS组大鼠中肝未损伤组[ALT为(66.75±7.12)U/L]和肝损伤组[ALT为(227.38±22.87)U/L]大鼠的肝脏样品进行代谢组学分析,筛选壮骨关节丸致特异质肝损伤可能易感生物标志物。结果:初步鉴定得到9个潜在相关易感生物标志物:L-鸟氨酸、肌苷、4-吡哆酸、黄素腺嘌呤二核苷酸、牛磺胆酸、花生四烯酸、视黄基酯、亚油酸和肌酸;涉及12条代谢通路,主要有亚油酸代谢、花生四烯酸代谢、视黄醇代谢、精氨酸和脯氨酸代谢4条通路。结论:壮骨关节丸特异致肝损伤易感机体在代谢层面有其潜在的易感生物标志物,为壮骨关节丸特异质肝损伤作用机制研究奠定生物学基础。Objective： To explore the serum metabolomics of Zhuanggu Guanjie Pill （ZGP）-induced idiosyncrasy liver injury. Methods： Rat model of immune stress-mediated idiosyncrasy liver injury was induced by caudal vein injection of lipopolysaccharide （LPS）. The ALT activity values of ZGP＋LPS group and LPS group was used as the index to evaluate the rats whether it is susceptible animal （ZGP＋LPS group^LPS group was not susceptible group which was liver without injury group; ZGP＋LPS group〉2 times of LPS group was strong susceptibility group which was liver with injury group; others were weak susceptible group）. The liver samples of rats in liver without injury group[ALT value was （66.75 ± 7.12）U/L）] and liver with injury group [ALT value was （227.38±22.87）U/L] in ZGP＋LPS group were detected by UPLC-QTOF/MS based on metabo^omics, to screen the possible susceptible biomarkers of ZGP-induced idiosyncrasy live injury. Results： Nine potential biomarkers were tentatively identified in the liver samples. They were L-ornithine, inosine, 4-pyridoxic acid, flavin adenine dinucleotide, taurocholic acid, arachidonic acid, retinyl ester, linoleic acid and creatine, respectively.It involved 12 metabolic pathways, among which there are four main pathways： linoleic acid metabolism, arachidonic acid metabolism, retinol metabolism, arginine and proline metabolism. Conclusion： The body susceptible to ZGP-induced idiosyncrasy liver injury has potential biomarkers at the metabolic level, which lays a biological foundation for the study of the mechanism of ZGP.

关 键 词：壮骨关节丸 特异致肝损伤 丙氨酸氨基转移酶 UPLC-QTOF/MS 代谢组学 

分 类 号：R285.5[医药卫生—中药学]