目的 研究肠道菌群失调对黄芩苷和黄芩素在大鼠体内药动学的影响。方法 将SD大鼠分为4组：黄芩苷组、抗生素+黄芩苷组、黄芩素组、抗生素+黄芩素组。利用盐酸林可霉素造模5 d，诱导大鼠肠道菌群失调。采用药动学相关技术和方法，正常大鼠和肠道菌群失调大鼠分别ig给予等摩尔剂量（370 μmol/kg）的黄芩苷和黄芩素，于20 h内不同时间点采集血浆样品，采用LC-MS/MS测定血浆中黄芩苷的浓度，绘制药时曲线，用DAS.2.2软件将所得数据进行分析处理，比较黄芩苷和黄芩素在正常大鼠和菌群失调大鼠体内的药动学行为变化。结果 黄芩素ig给药后，原型药完全被代谢，血浆中主要检测到代谢产物黄芩苷；与黄芩苷组达峰浓度[C_max，（16.35±9.48）mg/L]相比较，抗生素+黄芩苷组的C_max[（7.80±5.52）mg/L]显著降低，与黄芩苷组AUC_0~t[（75.16±48.40）mg·h/L]相比较，抗生素+黄芩苷组AUC_0~t[（32.60±18.88）mg·h/L]显著降低；与黄芩素组C_max[（60.39±56.32）mg/L]相比较，抗生素+黄芩素组的C_max[（10.28±5.57）mg/L]显著降低，与黄芩素组AUC_0~t[（212.51±101.25）mg·h/L]相比较，抗生素+黄芩素组的AUC_0~t[（71.67±54.49）mg·h/L]显著降低。结论 肠道菌群失调抑制黄芩苷和黄芩素的吸收。

Objective To study the effects of intestinal flora imbalance after ig administration on pharmacokinetic parameters of baicalin or baicalein in rats. Methods The SD rats were divided into four groups including baicalin group, antibiotic + baicalin group, baicalein group, and antibiotic + baicalein group. Traditional antibiotic medicine lincomyci were used to induce rats gut micro dysbiosis for 5 d. The pharmacokinetics of related technologies and methods were used, and the rats were administered with Moore dose (370 μmol/kg) of baicalin and baicalein. The plasma samples were collected at different time points within 20 h, and the concentration of baicalin was determined with LC-MS/MS, and the curve was drawn. The data were analyzed by DAS.2.2 software, comparison of baicalin and baicalein in animal behavior changes of rats in normal rats and antibiotics. Results The results showed that the baicalein was metabolized entirely and the metabolite baicalin was detected mainly in rat plasma after oral administration of baicalein. These results showed that the C_max[(7.80 ±5.52) mg/L] of baicalin in rats in antibiotic + baicalin group was decreased compared with that with baicalin alone[C_max (16.35 ±9.48) mg/L]. Meanwhile, the AUC_0~t of baicalin in antibiotic + baicalin group was 32.60 ±18.88 mg·h/L which was significantly lower than that in rats with baicalin alone[(75.16 ±48.40) mg·h/L]. These results showed that the C_max[(10.28 ±5.57) mg/L] of baicalin in rats of antibiotic + baicalein group was decreased compared with that with baicalein alone[C_max (60.39 ±56.32) mg/L]. Meanwhile, the AUC_0~t of baicalin in antibiotic + baicalein group was (71.67 ±54.49) mg·h/L which was significantly lower than that in rats with baicalein alone[(212.51 ±101.25) mg·h/L]. Conclusion Baicalin and baicalein showed bad pharmacokinetic behavior in rats when the rat intestinal flora is imbalance.

贵州省普通高等学校工程研究中心课题（黔教合KY字[2015]）