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2',3',5'-三氧乙酰基-N6-(3-羟基苯胺)腺苷(WS070117)是天然产物虫草素的衍生物,体内外实验证明它具有显著脂质调节活性,并且毒性低。本次研究采用基于NMR代谢组学方法评价不同剂量WS070117调血脂活性。高脂血地鼠用6个不同剂量的WS070117(3、12、50、100、200和400 mg·kg-1·d-1)治疗。采用主成分分析法(PCA)及正交偏最小二乘法-判别分析法(OPLS-DA)两种多变量方法分析地鼠血清氢图谱。结果表明,WS070117能有效调节高脂血地鼠脂代谢、胆碱代谢及糖代谢紊乱,且其效应与剂量呈正相关。3 mg·kg-1·d-1的WS070117具有微弱脂质调节活性,而12和50 mg·kg-1·d-1的WS070117都显著调节代谢物浓度向正常水平转归,当WS070117的剂量达到100 mg·kg-1·d-1时,它的脂质调节活性强于阳性对照药。结果表明,基于NMR代谢组学可能成为评价调血脂化合物剂量效应关系的有效方法。
The 2 ', 3', 5'-trioxyacetyl-N6- (3-hydroxyanilino) adenosine (WS070117) is a natural product of cordycepin derivatives and has been demonstrated in vitro and in vivo to have significant lipid- low. In this study, based on NMR metabonomics method to evaluate the different doses of WS070117 blood lipid regulating activity. Hyperlipidemic hamsters were treated with 6 different doses of WS070117 (3, 12, 50, 100, 200 and 400 mg · kg-1 · d-1). Principal component analysis (PCA) and orthogonal partial least squares - discriminant analysis (OPLS-DA) two kinds of multivariate analysis of hamster serum hydrogen profile. The results showed that WS070117 could effectively regulate lipid metabolism, cholinergic metabolism and glucose metabolism disorder in hyperlipidemic rats, and its effect was positively correlated with dose. WS070117 at 3 mg · kg-1 · d-1 had weak lipid-regulating activity, whereas WS070117 at 12 and 50 mg · kg-1 · d-1 significantly regulated the normalized level of metabolite concentration. When the dose of WS070117 When it reached 100 mg · kg-1 · d-1, its lipid-regulating activity was stronger than that of the positive control. The results show that NMR-based metabonomics may be an effective method to evaluate the dose-response relationship of lipid-lowering compounds.