评价淫羊藿低糖苷组分的安全性并研究其中5 种低糖苷成分的药代动力学。方法4 组KM 小鼠 分别灌胃玉米油溶媒以及1 968、2 625、3 500 mg·kg-1 淫羊藿低糖苷组分后，连续7 d 观察小鼠的毒性反应和 死亡情况，观察结束后解剖。计算各组小鼠的脏体比和脏脑比，ELISA 法测定血浆中谷丙转氨酶（ALT）和谷草 转氨酶（AST）的含量，苏木精-伊红（HE）染色法观察小鼠肝脏病理变化。C57BL/6J 小鼠分别尾静脉注射或灌胃 宝藿苷Ⅰ、宝藿苷Ⅱ、箭藿苷A、箭藿苷B 和箭藿苷C 后于不同时间点采血，超高效液相色谱-串联质谱 （UHPLC-MS/MS）法测定5 种低糖苷的血药浓度并计算药动学参数。结果与空白对照组相比，小鼠灌胃不同 剂量淫羊藿低糖苷组分后体质量、脏体比、脏脑比及血浆中ALT 和AST 含量均无显著性差异，肝脏病理切片 也无显著变化。静脉注射后，5 种低糖苷的药时曲线下面积（AUC0-t）分别为4.82、82.54、276.64、88.77、 178.02 min·μg·mL-1，半衰期（t1/2）分别为60.42、115.27、67.63、131.61、129.87 min。灌胃后，5 种低糖苷的 AUC0-t 分别为31.64、18.59、3.48、2.41、2.42 min·μg·mL-1，峰浓度（Cmax）分别为147.23、86.76、15.58、24.34、 26.12 ng·mL-1，达峰时间（tmax）分别为21.00、78.00、78.00、30.00、28.00 min。宝藿苷Ⅰ、宝藿苷Ⅱ、箭藿苷A、 箭藿苷B、箭藿苷C 口服生物利用度分别为1.91%、0.51%、0.05%、0.06%、0.04%。结论淫羊藿低糖苷组 分安全性高，在3 500 mg·kg-1 剂量下仍没有观察到肝毒性，其中5 种低糖苷成分在小鼠体内吸收快、消除快， 生物利用度低。

To evaluate the safety of the low glucoside composites of Epimedii Folium and clarify the pharmacokinetic characteristics of its five low glucosides. Methods Four groups of KM mice were orally administrated of corn oil，1 968，2 625 and 3 500 mg·kg-1 low glucoside composites of Epimedii Folium，respectively. Then，the living conditions，toxic symptoms，and death of the mice were observed for 7 consecutive days. After the mice were dissected， the viscera / body ratio and the viscera / brain ratio were calculated. Besides， the contents of alanine aminotransferase （ALT） and aspartate transaminase （AST） in plasma were determined by ELISA， and the pathological changes of the liver were observed by HE staining. C57BL / 6J mice were intravenously or orally administered of baohuoside I， baohuoside II， sagittatoside A， sagittatoside B and sagittatoside C. Then， blood samples were collected at different time points. The plasma concentrations of the five low glucosides were measured by UHPLC-MS/MS. Results When compared with the control group， no significant differences were found in the body mass，viscera/body ratio，viscera/brain ratio，contents of ALT and AST in plasma after oral administration of different doses of low glucoside composites to mice. Moreover，no pathological changes or damages were found in the liver sections. After intravenous injection， the AUC0-t values of baohuosideⅠ， baohuoside Ⅱ， sagittatoside A， sagittatoside B and sagittatoside C in mice were 4.82，82.54，276.64，88.77 and 178.02 min·μg·mL-1，respectively. Meanwhile， the t1/2 values were 60.42， 115.27， 67.63， 131.61 and 129.87 min， respectively. After oral administration，the AUC0-t values of the five low glucosides were 31.64，18.59，3.48，2.41 and 2.42 min·μg·mL-1， respectively. The Cmax values were 147.23，86.76，15.58，24.34 and 26.12 ng·mL-1，respectively. The tmax values were 21.00， 78.00， 78.00， 30.00 and 28.00 min， respectively. The bioavailability of baohuosideⅠ， baohuoside Ⅱ，sagittatoside A sagittatoside B and sagittatoside C were 1.91%，0.51%，0.05%，0.06% and 0.04%，respectively. Conclusion The low glucoside composites of Epimedii Folium has high safety，and no hepatotoxicity were observed at dose of 3 500 mg·kg-1. The 5 low glucosides are quickly absorbed and rapidly eliminated in mice，and all of them have low bioavailability.

R285.5

国家科技重大专项课题（2017ZX09301051）；国家自然科学基金国际（地区）合作研究项目（81961128028）；广东省自然科学基金杰出 青年项目（2022B1515020079）；广州中医药大学“双一流”与高水平大学学科协同创新团队项目（2021xk77）；广东省“岭南中医药”现代化基金 项目（2020B1111100004）；2020年广东省科技创新战略专项资金（粤港澳联合实验室）项目（2020B1212030006）。