目的 采用1H-NMR代谢组学技术比较文拉法辛、帕罗西汀和圣约翰草提取物3种药物对大鼠内源性代谢物轮廓的影响,探讨其作用机制的差异性。方法 采用3种药物对慢性不可预知应激(CUMS)动物模型进行干预,收集大鼠血清样本,进行1H-NMR代谢组学分析、获得差异物代谢轮廓。结果 代谢组学分析结果显示,3种抗抑郁药物对CUMS模型大鼠血清中内源性代谢产物影响差异较大,对差异代谢物的回调程度有所不同,其中文拉法辛可回调6种、帕罗西汀可回调4种、圣约翰草提取物可回调5种,且乳酸、胆碱、N-乙酰糖蛋白是3个药物共同回调的。结论 不同的药物对内源性代谢物的调节种类和程度既具有差异性,也具有相似性,可为抗抑郁药物作用机制研究提供参考。
Abstract
OBJECTIVE To explore the mechanism of venlafaxine, paroxetine and St. John's wort extract by comparing the changes of endogenous metabolites profile in rat serum. METHODS These three drugs were employed to intervene in rats exposed to the chronic unpredictable mild stress (CUMS). Serum samples from all of rats were collected for a 1H-NMR metabolomics analysis to find the differences of metabolic profile. RESULTS The resulting metabolic profiles demonstrated that these three antidepressants have an obvious difference effect on the endogenous metabolites in serum of the CUMS rats. It was also shown that the differential metabolites could be reversed in different degree. Six metabolites could be callback by venlafaxine while 4 metabolites by paroxetine and five metabolites by St. John's wort extract, in which lactate, choline, N-acetyl glycoprotein could be regulated to normal by all these three drugs. CONCLUSION The different drugs have difference regulation on the type and level of the endogenous metabolites, but also have similarities, which can provide a reference for the better understanding of the mechanism of antidepressant drugs.
关键词
文拉法辛 /
帕罗西汀 /
圣约翰草提取物 /
慢性温和不可预知应激模型 /
代谢组学
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Key words
venlafaxine /
paroxetine /
St.John'swort extract /
chronic unpredictable mild stress /
metabolomics
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中图分类号：
R965
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脚注
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基金
国家自然科学基金资助项目(81441096)
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