基于对药动学及血清SCFAs的影响研究葛根芩连汤对腹泻小型猪的作用＊

目的 通过研究葛根芩连汤（Gegenqinlian decoction,GQD）在腹泻小型猪给药期间其功效成分药动学特征及其对血清短链脂肪酸（short-chain fatty acids,SCFAs）的影响,探讨方药对腹泻机体的作用。方法 正常和腹泻小型猪连续4天给予GQD,不同时间点采血,UPLC-MS/MS测定10个主要功效成分的血浆含量,计算药动学参数;GC-MS检测血清SCFAs含量。结果 GQD给药期间小型猪腹泻症状显著减轻;0 h-48 h葛根素、大豆苷元、黄芩苷、黄芩素和汉黄芩素在腹泻小型猪体内血药水平显著高于正常组,48 h-96 h这些成分血药浓度逐渐递减至正常水平,提示腹泻改变GQD成分药动学行为;腹泻小型猪血清中肠道菌群代谢产物SCFAs含量较正常组显著降低,给药后恢复至正常,提示对肠道微生态调整作用。结论 GQD给药期间其功效成分药动学及其血清SCFAs的变化可部分反映方药对腹泻机体的康复过程,为其临床应用提供了实验依据。

Effect of Gegenqinlian Decoction on Diarrheal Miniature Pigs was Studied Basing on the Change of Pharmacokinetics and Serum SCFAs

Objective To investigate the effect of Gegen Qinlian decoction (GQD) on the diarrheal mini-pigs by pharmacokinetics and its effect on the short-chain fatty acids (SCFAs) in serum during the treatment.Methods After treatment with GQD for four days in normal and diarrheal mini-pigs, blood samples were collected at different time points. Ten bioactive components of GQD in plasma were detected by UPLC-MS/MS to investigate its pharmacokinetics. Levels of serum SCFAs were detected by GC-MS.Results Diarrheal symptoms in mini-pigs were remarkably alleviated during GQD treatment. In 0 h-48 h, plasma levels of puerarin, daidzin, baicalin, baicalein, and wogonin in the diarrheal group were higher than in the normal group, which suggests that diarrhea alters the pharmacokinetics of components of GQD. In 48 h-96 h, plasma concentrations of these ingredients in the diarrheal group were gradually decreased to the normal levels. Moreover, serum levels of SCFAs, metabolites of gut microbiota, were significantly reduced in the diarrheal group, and GQD reversed this change after treatment, indicating the modulating of intestinal micro-ecology.Conclusion Pharmacokinetics of ingredients from GQD and its effect on serum SCFAs could partially reflect the healing process of mini-pig diarrhea, which might provide evidence for its clinical efficacy.