甲巯咪唑片干预大鼠甲亢模型的代谢组学研究

Serum Metabonomics in Hyperthyroid Model Intervened by Thiamazole Tablets

目的本实验采用血清代谢组学技术探讨甲巯咪唑片在干预大鼠皮下注射L-左甲状腺素钠诱导甲亢模型的作用机制研究。方法选用SD大鼠35μg·100 g^(-1)皮下注射L-左甲状腺素钠造模7 d后,灌胃给予21 mg·kg^(-1)的甲巯咪唑片混悬液21 d,同时以模型和正常大鼠作为对照,采用UPLC-QTOF-MS技术对不同组别大鼠的血清进行分析。结果造模后,与正常组大鼠相比,甲亢大鼠体内的草酰乙酸、磷酸二羟基丙酮、乙基葡糖苷酸、白三烯、羟基犬尿氨酸、甘油三酯和溶血磷脂呈显著上升趋势,而甘油二酯、磷脂酰肌醇呈显著下降趋势。甲巯咪唑片干预21 d后,大鼠体内草酰乙酸、磷酸二羟基丙酮、白三烯等的物质代谢水平接近正常状态。结论推测甲亢大鼠机体内的三羧酸循环发生障碍,代谢出现紊乱,给予甲巯咪唑片后紊乱得到一定的改善。

OBJECTIVE To investigate the mechanism of hyperthyroid rats treated by thiamazole tablets by the serum metabonomics technology. METHODS Hyperthyroid rats were modeled by subcutaneous injection of L-levothyroxine sodium 35 μg ·100g（-1） for 7 d. Then rats of thiamazole-treated group were treated by intragastric administration of thiamazole tablets suspension 21 mg·kg（-1）for 21 d. The serum levels of model rats,control rats,thiamazole-treated rats were analyzed by using UPLC-QTOF-MS and UPLCQTOF-MS was combined with two different modes of positive and negative ions as well as KEGG and HMDB. RESULTS Compared with normal rats,among hyperthyroid rats oxalacetic acid,dihydroxyacetone phosphate（ DHAP）,ethyl glucuronide,leukotriene E3,hydroxykynurenine,triglycerides（ TG） and lysophospholipids were increased. Meanwhile,diacylglycerol（ DG） and phosphatidylinositol（ PI） were decreased. The 21 d later,the metabolism levels of oxalacetic acid,dihydroxyacetone phosphate,leukotriene E3,phospholipids and fatty acids in thiamazole-treated rats were close to the normality. CONCLUSION The results infer that tricarboxylic acid cycle of hyperthyroid rat is disturbed： all of glucose metabolism,lipid metabolism and amino acid metabolism get into disorder.And these disorders are improved certainly by treating thiamazole. Meanwhile,this method provides an available reference for the establishment of the means of diagnosing hyperthyroidism based on metabonomics and the assessment of the therapeutic effect of thiamazole tablets.