基于代谢组学的六味地黄丸干预大鼠甲亢模型的作用研究  

Serum metabonomic study on liuwei dihuang pills in the treatment of hyperthyroidism

作　　者：王彬[1,2] 沈岚[1,2] 从文娟[1] 朱云云[1] 王强[1,2] 冯怡[1] 

机构地区：[1]上海中医药大学中药现代制剂技术教育部工程中心,上海201203 [2]上海中医药大学中药学院,上海201203

出　　处：《中国药理学通报》2013年第5期632-637,共6页Chinese Pharmacological Bulletin

基　　金：国家科技重大专项(重大新药创制)(No 2009ZX09502-009);国家自然科学基金项目;上海市教委重点学科自然基金(No J50302);上海市科委2012年度"科技创新行动计划"(No 12401900402);上海市教委创新项目(No12ZZ124);上海高校青年教师专项科研基金(NoSzy11022);上海市教委预算内科研项目(No 2011JS27)

摘　　要：目的该文采用血清代谢组学探讨正常大鼠皮下注射L-左旋甲状腺素钠诱导甲亢模型的作用机制和六味地黄丸干预甲亢模型的作用研究。方法选用SD大鼠按35μg.(100 g)-1皮下注射L-左旋甲状腺素钠造模1周后,给予4.7 g.kg-1的六味地黄丸干预3周,同时以正常大鼠作为对照,采用UPLC-QTOF-MS技术对不同组别大鼠的血清进行了分析。结果甲亢大鼠的体内草酰乙酸、磷酸二羟基丙酮、乙基葡糖苷酸、甘油三酯、溶血磷脂、胆固醇等明显上调;而六味地黄丸干预后,这些物质的水平出现明显下调。结论推测甲亢大鼠机体内的三羧酸循环发生障碍,糖、脂质、氨基酸代谢均出现紊乱,给予六味地黄丸后紊乱得到一定的改善。同时,这种方法为全面建立一种基于代谢组学的手段来诊断甲亢的病因和评价六味地黄丸治疗作用,提供一定的参考。Aim To explore the underlying mechanism of hyperthyroidism induced by subcutaneous injection of L-levothyroxine sodium and and intervention effects of Liuwei Dihuang pills on sprague dawley rats via serum metabolomics. Methods After rats were injected with L-levothyroxine sodium at a dosage of 35 μg · （100 g） ^-1 every day for 1 week, and then Liuwei dihuang pills （LDPs） were treated at a dose of 4. 7 g · kg-1 for 3 consecutive weeks. The serum samples for rats were obtained after the treatment of LDPS and the metabolic profiles of serum were obtained with ultra performance liquid chromatography coupled with time- of-flight mass spectrometry （ UPLC-QTOF-MS ）. Resuits The levels of oxaloacetic acid, Dihydroxyacetone phosphate （DHAP）, ethyl glucuronide, triglyceride, lysophospholipids and cholesterol were significantly increased in the model group as compared to the normal rats. Moreover, these levels could be regulated to be close to normal after the treatment of LDPS. Conclusions There is severe disturbance in the tricarboxylic acid cycle as well as sugar and lipid metabolism for hyperthyroidism rats. LDPS can exhibite obvious effects on the treatment of hyperthyroidism. Serum metabonomics analysis reveals the changes of metabolites traits during the treatment of LDPS, thus providing a supplementary evaluation method of LDPS in the treatment of hyperthyroidism.

关 键 词：六味地黄丸 UPLC-QTOF-MS 代谢紊乱 三羧酸循环 甲亢阴虚 代谢组学 生物标志物 

分 类 号：R-332[医药卫生] R282.71