外翻肠囊法考察盐酸小檗胺对盐酸小檗碱肠吸收特性的影响
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摘要
目的:研究正常环境和高钙环境下,大鼠不同肠段中盐酸小檗胺对盐酸小檗碱肠吸收特性的影响。方法:采用大鼠外翻肠囊模型,通过HPLC检测不同配伍组外翻肠囊吸收液中盐酸小檗碱的含量,对不同配伍组的单位面积吸收量进行单因素方差分析。结果:与相同时间点正常J70组(正常环境,盐酸小檗碱质量浓度70 mg·L~(-1))比较,120 min时正常J70+Ver100组(正常环境,盐酸小檗碱质量浓度70 mg·L~(-1),加入盐酸维拉帕米质量浓度100 mg·L~(-1))的单位面积吸收量在回肠段显著增加(P<0.05); 30,60,90 min时高钙J70+A35组(高钙环境,盐酸小檗碱质量浓度70 mg·L~(-1),加入盐酸小檗胺质量浓度35 mg·L~(-1))在十二指肠的单位面积吸收量显著增加(P<0.05); 30,90,120 min时高钙J70+A70组(高钙环境,盐酸小檗碱质量浓度70 mg·L~(-1),加入盐酸小檗胺质量浓度70 mg·L~(-1))在回肠的单位面积吸收量显著增加(P<0.05)。相较于相同质量浓度的正常组,高钙J70+A35组、高钙J70+A70组中盐酸小檗碱的肠吸收更好。结论:盐酸小檗胺在一定程度上对盐酸小檗碱的吸收具有促进作用,尤其是在高钙环境下。
Objective:To investigate the effect of berbamine hydrochloride on the absorption characteristics of berberine hydrochloride in different intestinal segments of rats in normal environment and high calcium environment.Method:Taking rat everted intestinal sac model,the content of berberine hydrochloride in absorbent solution of everted intestinal sac from different compatibility groups was determined by HPLC,and the uptake per unit area in different groups was analyzed by One-way ANOVA.Result:Compared with the normal J70 group(in normal environment,the concentration of berberine hydrochloride was 70 mg·L~(-1)) at the same time point,the uptake per unit area of the normal J70 + Ver100 group(in normal environment,the concentration of berberine hydrochloride was 70 mg·L~(-1),adding verapamil hydrochloride to a concentration of 100 mg·L~(-1)) was significantly increased in the ileum(P<0.05) at 120 min;the uptake per unit area values of the high calcium J70 + A35 group(in high calcium environment,the concentration of berberine hydrochloride was 70 mg·L~(-1),adding berbamine hydrochloride to a concentration of 35 mg·L~(-1)) were significantly increased in the duodenum(P<0.05) at 30,60,90 min;and the uptake per unit area values of the high calcium J70 + A70 group(in high calcium environment,the concentration of berberine hydrochloride was 70 mg·L~(-1),adding berbamine hydrochloride to a concentration of 70 mg·L~(-1)) were significantly increased in the ileum(P<0.05) at 30,90,120 min.By comparing with the normal group with the same mass concentration,the intestinal absorption of berberine hydrochloride was better in the high calcium J70 + A35 group and the high calcium J70 + A70 group.Conclusion:Berbamine hydrochloride can promote the absorption of berberine hydrochloride in intestine to a certain extent,especially in the high calcium environment.
Objective:To investigate the effect of berbamine hydrochloride on the absorption characteristics of berberine hydrochloride in different intestinal segments of rats in normal environment and high calcium environment.Method:Taking rat everted intestinal sac model,the content of berberine hydrochloride in absorbent solution of everted intestinal sac from different compatibility groups was determined by HPLC,and the uptake per unit area in different groups was analyzed by One-way ANOVA.Result:Compared with the normal J70 group(in normal environment,the concentration of berberine hydrochloride was 70 mg·L~(-1)) at the same time point,the uptake per unit area of the normal J70 + Ver100 group(in normal environment,the concentration of berberine hydrochloride was 70 mg·L~(-1),adding verapamil hydrochloride to a concentration of 100 mg·L~(-1)) was significantly increased in the ileum(P<0.05) at 120 min;the uptake per unit area values of the high calcium J70 + A35 group(in high calcium environment,the concentration of berberine hydrochloride was 70 mg·L~(-1),adding berbamine hydrochloride to a concentration of 35 mg·L~(-1)) were significantly increased in the duodenum(P<0.05) at 30,60,90 min;and the uptake per unit area values of the high calcium J70 + A70 group(in high calcium environment,the concentration of berberine hydrochloride was 70 mg·L~(-1),adding berbamine hydrochloride to a concentration of 70 mg·L~(-1)) were significantly increased in the ileum(P<0.05) at 30,90,120 min.By comparing with the normal group with the same mass concentration,the intestinal absorption of berberine hydrochloride was better in the high calcium J70 + A35 group and the high calcium J70 + A70 group.Conclusion:Berbamine hydrochloride can promote the absorption of berberine hydrochloride in intestine to a certain extent,especially in the high calcium environment.
引文
[1]熊燕,林瑗.糖尿病并发症的研究进展[J].中国医师杂志,2017,19(10):1441-1449.
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[13]吴林霖,李梅,巩仔鹏,等.基于大鼠离体外翻肠囊模型考察杜仲提取物在正常和自发性高血压状态下的肠吸收特性差异[J].中国实验方剂学杂志,2018,24(9):15-21.
[14]黄斌,陈晓萌,张迎春,等.元胡止痛方肠吸收液对大鼠离体胸主动脉环张力的影响[J].中国实验方剂学杂志,2012,18(5):117-120.
[15]秦海蛟,柳梦婷,唐力英,等.肠外翻囊法研究淫羊藿肠吸收成分及其吸收特征[J].中国实验方剂学杂志,2015,21(22):163-168.
[16]SA C L,LV H,BA Y Y,et al.The effects o notoginsenoside R1on the intestinal absorption o geniposide by the everted rat gut sac model[J].JEthnopharmacol,2012,142(1):136-143.
[17]YANG H L,YI X Z,LI L,et al.Estimation of the iron absorption from ferrous glycinate-loaded solid lipid nanoparticles by rat everted intestinal sac model[J].Food Sci Technol Res,2017,23(4):567-573.
[18]MA Y G,ZHANG Y B,BAI Y G,et al.Berberine alleviates the cerebrovascular contractility in streptozotocin-induced diabetic rats through modulation of intracellular Ca2+handling in smooth muscle cells[J].Cardiovasc Diabetol,2016,doi:10.1186/s12933-016-0382-9.
[19]Maeng H J,Yoo H J,Kim I W,et al.P-glycoproteinmediated transport of berberine across Caco-2 cell monolayers[J].J Pharm Sci,2002,91(12):2614-2621.
[20]曾凤.小檗胺对兔急性高眼压视网膜损伤保护作用的实验研究[J].衡阳:南华大学,2010.
[21]何浩,何海鹰,张家萍,等.小檗胺对大鼠糖尿病性白内障模型中DNA损伤修复及致障过程的影响[J].中国生物化学与分子生物学报,1998,14(3):300-303.
[22]Sankaranarayanan C,Nishanthi R,Pugalendi P.Ameliorating effect of berbamine on hepatic key enzymes of carbohydrate metabolism in high-fat diet and streptozotocin induced type 2 diabetic rats[J].Biomed Pharmacother,2018,103:539-545.
[23]何玉玲,梁瑜祯.内分泌疾病与钙代谢异常[J].临床内科杂志,2013,30(3):152-153.
[24]王婷,刘振国,张粉利,等.2型糖尿病患者血清钙浓度异常及其与糖化血红蛋白的关系[J].临床内科杂志,2016,33(4):265-266.
[2]陈丹丹,帅天姣,李娟,等.糖尿病视网膜病变微血管神经病变发病机制的研究进展[J].国际眼科杂志,2018,18(5):844-846.
[3]ZHANG L X,LONG J Y,JIANG W S,et al.Trends in chronic kidney disease in China[J].N Engl J Med,2016,375(9):905-906.
[4]李骋,何金枝,周学东,等.黄连素调控胰岛素抵抗相关2型糖尿病的研究进展[J].中国中药杂志,2017,42(12):2254-2260.
[5]PANG B,ZHAO L H,ZHOU Q,et al.Application of berberine on treating type 2 diabetes mellitus[J].Int JEndocrinol,2015,doi:10.1155/2015/905749.
[6]胡诚毅,莫志贤.黄连素的药理作用及机制研究进展[J].中国实验方剂学杂志,2017,23(20):213-219.
[7]ZHANG M,CHEN L.Berberine in type 2 diabetes therapy:a new perspective for an old antidiarrheal drug?[J].Acta Pharm Sin B,2012,2(4):379-386.
[8]Fratter,Servi B D.New oral delivery system to improve absorption of berberine:likely interaction of cationized chitosan with PG-P pump[J].Int J Drug Deliv Tec,2014,5(1):33-42.
[9]王广基.药物代谢动力学[M].北京:化学工业出版社,2005:38.
[10]PAN G Y,WANG G J,LIU X D,et al.The involvement of P-glycoprotein in berberine absorption[J].Pharmacol Toxicol,2002,91(4):193-197.
[11]LIU C S,ZHENG Y R,ZHANG Y F,et al.Research progress on berberine with a special focus on its oral bioavailability[J].Fitoterapia,2016,109:274-282.
[12]赵艳玲,李柏岩,乔国芬,等.小檗胺对ROCC介导的血管平滑肌细胞内游离钙的影响[J].中国药理学通报,2000,16(4):450-452.
[13]吴林霖,李梅,巩仔鹏,等.基于大鼠离体外翻肠囊模型考察杜仲提取物在正常和自发性高血压状态下的肠吸收特性差异[J].中国实验方剂学杂志,2018,24(9):15-21.
[14]黄斌,陈晓萌,张迎春,等.元胡止痛方肠吸收液对大鼠离体胸主动脉环张力的影响[J].中国实验方剂学杂志,2012,18(5):117-120.
[15]秦海蛟,柳梦婷,唐力英,等.肠外翻囊法研究淫羊藿肠吸收成分及其吸收特征[J].中国实验方剂学杂志,2015,21(22):163-168.
[16]SA C L,LV H,BA Y Y,et al.The effects o notoginsenoside R1on the intestinal absorption o geniposide by the everted rat gut sac model[J].JEthnopharmacol,2012,142(1):136-143.
[17]YANG H L,YI X Z,LI L,et al.Estimation of the iron absorption from ferrous glycinate-loaded solid lipid nanoparticles by rat everted intestinal sac model[J].Food Sci Technol Res,2017,23(4):567-573.
[18]MA Y G,ZHANG Y B,BAI Y G,et al.Berberine alleviates the cerebrovascular contractility in streptozotocin-induced diabetic rats through modulation of intracellular Ca2+handling in smooth muscle cells[J].Cardiovasc Diabetol,2016,doi:10.1186/s12933-016-0382-9.
[19]Maeng H J,Yoo H J,Kim I W,et al.P-glycoproteinmediated transport of berberine across Caco-2 cell monolayers[J].J Pharm Sci,2002,91(12):2614-2621.
[20]曾凤.小檗胺对兔急性高眼压视网膜损伤保护作用的实验研究[J].衡阳:南华大学,2010.
[21]何浩,何海鹰,张家萍,等.小檗胺对大鼠糖尿病性白内障模型中DNA损伤修复及致障过程的影响[J].中国生物化学与分子生物学报,1998,14(3):300-303.
[22]Sankaranarayanan C,Nishanthi R,Pugalendi P.Ameliorating effect of berbamine on hepatic key enzymes of carbohydrate metabolism in high-fat diet and streptozotocin induced type 2 diabetic rats[J].Biomed Pharmacother,2018,103:539-545.
[23]何玉玲,梁瑜祯.内分泌疾病与钙代谢异常[J].临床内科杂志,2013,30(3):152-153.
[24]王婷,刘振国,张粉利,等.2型糖尿病患者血清钙浓度异常及其与糖化血红蛋白的关系[J].临床内科杂志,2016,33(4):265-266.