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肠淋巴吸收及其对大鼠中柚皮苷和柚皮素药代动力学的影响。

Mesenteric lymphatic absorption and the pharmacokinetics of naringin and naringenin in the rat.

机构信息

Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.

出版信息

J Agric Food Chem. 2012 Dec 26;60(51):12435-42. doi: 10.1021/jf301962g. Epub 2012 Dec 14.

Abstract

The hypothesis for this study was that flavanoids and their glycoside are absorbed mainly through the portal vein to enter the liver for biotransformation and are only partially absorbed through the lymphatic duct. To verify this hypothesis, an unconscious, mesenteric lymphatic/portal vein/jugular vein/bile duct/duodenum-cannulated rat model was developed. Naringin was administered at dosages of 600 and 1000 mg/kg, and naringenin was given at 100 and 300 mg/kg by intraduodenal administration. Blood samples collected from the portal vein and jugular vein as well as lymphatic fluid were prepared by protein precipitation and then analyzed by high-performance liquid chromatography with photodiode array detection (HPLC-DAD). Analyses of these samples were doubly confirmed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The results show that, after intraduodenal administration, both compounds were mainly absorbed into portal blood rather than mesenteric lymph, and most of the intact analyte would be eliminated through bile excretion. The area under the concentration (AUC) ratio was defined to represent the absorption ratio for portal vein [AUC(portal)/AUC((portal+lymph))] and lymph fluid [AUC(lymph)/AUC((portal+lymph))]. The results indicate that the portal and lymphatic absorptions for naringin were around 95 and 5.0%, respectively. The respective absorptions for naringenin were around 98 and 2%, respectively.

摘要

本研究的假设是,类黄酮及其糖苷主要通过门静脉吸收进入肝脏进行生物转化,只有部分通过淋巴导管吸收。为了验证这一假设,建立了一种无意识的肠系膜淋巴/门静脉/颈静脉/胆管/十二指肠插管大鼠模型。通过十二指肠给药,给予柚皮苷 600 和 1000mg/kg,给予柚皮素 100 和 300mg/kg。从门静脉和颈静脉以及淋巴液中采集的血液样本通过蛋白质沉淀制备,然后通过高效液相色谱-光电二极管阵列检测(HPLC-DAD)进行分析。通过液相色谱-串联质谱(LC-MS/MS)对这些样品进行了双重确认。结果表明,十二指肠给药后,两种化合物主要被吸收进入门静脉血液,而不是肠系膜淋巴,大部分完整的分析物将通过胆汁排泄。定义面积下浓度(AUC)比表示门静脉[AUC(门静脉)/AUC((门静脉+淋巴))]和淋巴液[AUC(淋巴)/AUC((门静脉+淋巴))]的吸收比。结果表明,柚皮苷的门静脉和淋巴吸收分别约为 95%和 5.0%。柚皮素的吸收分别约为 98%和 2%。

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