丹皮酚在肝癌前病变大鼠体内的药动学研究  

Study on pharmacokinetics of Paeonol( Pae) in hepatic precancerous lesion model in rats

作　　者：宋艺君[1] 杨史军 王湘[3] 张东星[3] 李京涛[1] 蔡大勇[2] 王玥琦[3] 

机构地区：[1]陕西中医药大学,陕西咸阳712046 [2]中国医学科学院药用植物研究所 [3]北京中医药大学

出　　处：《中西医结合肝病杂志》2018年第1期37-40,I0002,共5页Chinese Journal of Integrated Traditional and Western Medicine on Liver Diseases

基　　金：国家自然科学基金项目(No.81603612);陕西中医药大学科研基金项目(No.2015PY12)

摘　　要：目的:建立测定大鼠血浆中丹皮酚浓度的高效液相方法(HPLC),并研究丹皮酚在肝癌前病变大鼠病程不同阶段的药动学。方法:给予大鼠二-乙基亚硝胺(DEN)腹腔注射,造模成功后,单次灌胃丹皮酚,于不同时间点眼眶取血,超高效液相色谱测定丹皮酚的血药浓度,运用Win Nonlin软件计算药动学参数;采用免疫组化法测定雌激素硫酸转移酶(EST)在大鼠肝、肾组织中的表达。结果:丹皮酚低剂量组:由d_(000)-d_(028)-d_(056)-d_(112),药物-时间曲线下面积(AUC)依次增加,最大血药浓度(Cmax)依次增加,总体清除率(CL)依次降低,分布容积(V)依次降低,平均滞留时间(MRT)依次降低;中剂量组:由d_(000)-d_(028)-d_(056)-d_(112),AUC依次增加,C_(max)依次增加,V依次降低,MRT依次降低,由d_(000)-d_(028)-d_(056),CL降低,由d_(056)-d_(112),CL增加;高剂量组:由d_(000)-d_(028)-d_(056)-d_(112),AUC依次增加,C_(max)依次增加,CL依次降低,V依次降低,MRT依次降低。肝脏内皮细胞和肾上皮细胞EST增加,肝细胞EST减少。结论:本实验所建立的HPLC方法操作简便、快速、专属性强,可用于丹皮酚血药浓度分析及其药代动力学研究。Objective：To develop a HPLC method for the determination of the concentration of Pae in rat plasma, and to study the phar- macokineties of Pae in different stages of hepatic precancerous lesion model. Methods ： Rats were successful modeling after given diethylnitro- samine（DEN） , given single Pae by oral, blood taken from orbital at different time points, determined concentration of Pae by UPLC, the pharmacokinetic parameters were calculated by WinNonlin software; the expression of Estrogen Sulfate Transferase （EST） protein in liver and kidney were detected by immunohistochemistry. Results：Low dose group of Pae： from do0o -d02s -d056 -d112, AUC, Cm^x increased in turn, CL,V,MRT decreased in turn; middle dose group of Pae： from d000 -d^2s -do56 -d112, AUC, C~~ increased in turn, V, MRT decreased in turn, from d000 -d028 -d056, CL decreased in turn, from d056 -d112, CL increased; high dose group of Pae： from d000 -d028 -d05 6 -d112, AUC, Cmax increased in turn, CL, V, MRT decreased in turn. EST increased in liver endothelial cells and renal epithelial cells, decreased in liver cells. Conclusion： A simple and specific HPLC method for the analysis of Pae was successfully developed and applied to a pharmaeokinetie study in rat plasma.

关 键 词：丹皮酚 肝癌前病变 雌激素硫酸转移酶 药动学 免疫组化 

分 类 号：R285.5[医药卫生—中药学]