盐炙对补骨脂丸中2种成分在脾肾阳虚泄泻大鼠体内药动学的影响  

Effects of stir-frying with salt-water on the in vivo pharmacokinetics of two constituents in Buguzhi Pills in diarrhea rats due to Spleen-kidney Yang Deficiency

作　　者：周宁[1] 王金金[1] 李红伟[1,2] 张振凌 李凯[1,2] ZHOU Ning;WANG Jin-jin;LI Hong-wei;ZHANG Zhen-ling;LI Kai(Henan University of Chinese Medicine,Zhengzhou 450046,China;Henan Provincial Research Center for Special Processing Technology of Chinese Medicine,Zhengzhou 450046,China)

机构地区：[1]河南中医药大学,河南郑州450046 [2]河南省中药特色炮制技术工程研究中心,河南郑州450046

出　　处：《中成药》2022年第11期3422-3427,共6页Chinese Traditional Patent Medicine

基　　金：国家自然科学基金面上项目(81873005);河南省高校科技创新人才支持计划(21HASTIT047);河南省高等学校青年骨干教师培养计划(2018GGJS083)。

摘　　要：目的考察盐炙对补骨脂丸中补骨脂素、异补骨脂素在脾肾阳虚泄泻大鼠体内药动学的影响。方法通过灌胃给予氢化可的松注射液(15 mg/kg)和冰番泻叶水煎液(10 g/kg)建立脾肾阳虚泄泻模型。大鼠随机分为空白组(生理盐水)、补骨脂丸组(8 g/kg)及模拟补骨脂丸Ⅰ~Ⅲ组(盐补骨脂+生小茴香、生补骨脂+盐小茴香、生补骨脂+生小茴香,8 g/kg),于0.083、0.17、0.25、0.5、0.75、1、1.5、2、3、5、7、9、12、24 h采血,HPLC法测定补骨脂素、异补骨脂素血药浓度,计算主要药动学参数。结果与模拟补骨脂丸Ⅲ组比较,补骨脂丸组、模拟补骨脂丸Ⅰ组补骨脂素、异补骨脂素C_(max)、AUC_(0~t)、AUC_(0~∞)升高(P<0.05,P<0.01),T_(max)延长(P<0.05,P<0.01),CL_(Z/F)降低(P<0.01),补骨脂丸组2种成分MRT_(0~∞)延长(P<0.05,P<0.01);模拟补骨脂丸Ⅱ组补骨脂素CL_(Z/F)降低(P<0.05),异补骨脂素AUC_(0~t)升高(P<0.01)。结论补骨脂丸中补骨脂、小茴香盐炙后,补骨脂素、异补骨脂素体内吸收提高,代谢减慢,从而可增强止泻作用。AIM To investigate the effects of stir-frying with salt-water on the in vivo pharmacokinetics of psoralen and isopsoralen in Buguzhi Pills in diarrhea rats due to Spleen-kidney Yang Deficiency.METHODS The model for diarrhea due to Spleen-kidney Yang Deficiency was established by intragastric administration of Hydrocortisone Injection(15 mg/kg)and iced Sennae Folium water decoction(10 g/kg).Rats were randomly assigned into blank group(normal saline),Buguzhi Pills group(8 g/kg)and simulated Buguzhi Pills groupsⅠ-Ⅲ(salt-processed Psoraleae Fructus+raw Foeniculif Fructus,raw Psoraleae Fructus+salt-processed Foeniculif Fructus,raw Psoraleae Fructus+raw Foeniculif Fructus,8 g/kg),after which blood collection was made at 0.083,0.17,0.25,0.5,0.75,1,1.5,2,3,5,7,9,12,24 h,HPLC was adopted in the plasma concentration determination of psoralen and isopsoralen,and main pharmacokinetic parameters were calculated.RESULTS Psoralen and isopsoralen in the Buguzhi Pills group and simulated Buguzhi Pills groupⅠdemonstrated increased C_(max),AUC_(0-t),AUC_(0-∞)(P<0.05,P<0.01),prolonged T_(max)(P<0.05,P<0.01)and decreased CL_(Z/F)(P<0.01)as compared with those in the simulated Buguzhi Pills groupⅢ,and these two constituents in the Buguzhi Pills group displayed prolonged MRT_(0-∞)(P<0.05,P<0.01).Reduced CL_(Z/F) for psoralen(P<0.05)and elevated AUC_(0-t) for isopsoralen(P<0.01)were observable in the simulated Buguzhi Pills groupⅡ.CONCLUSION After Psoraleae Fructus and Foeniculif Fructus in Buguzhi Pills are processd by stir-frying with salt-water,psoralen and isopsoralen exhibit enhanced in vivo absorption and slowed down metabolism,and thus can strengthen the anti-diarrheal effect.

关 键 词：补骨脂丸 补骨脂素 异补骨脂素 盐炙 泄泻 脾肾阳虚 体内药动学 HPLC 

分 类 号：R969.1[医药卫生—药理学]