淫羊藿苷及其代谢产物在骨质疏松模型大鼠肾脏组织中的分布
|
摘要
目的:探索骨质疏松模型大鼠灌胃给予淫羊藿苷后淫羊藿苷及其代谢产物在肾脏中分布情况。方法:按118mg·kg-1灌胃给予骨质疏松模型大鼠淫羊藿苷单体,分别于40 min,1.5,2.5,4,12,24 h取出肾脏组织,经生物样品预处理后,采用HPLC测定肾脏中淫羊藿苷及其代谢产物(淫羊藿次苷Ⅰ、淫羊藿次苷Ⅱ、淫羊藿素)的质量浓度,流动相0.4%乙酸水溶液(A)-甲醇(B)梯度洗脱(0~11 min,43%A;12~30 min,37%A;31~46 min,43%A),检测波长270 nm。结果:给药40 min后,在肾脏组织中检测到淫羊藿苷(0.017 5 mg·L-1)淫羊藿次苷Ⅰ(0.014 2 mg·L-1)及淫羊藿次苷Ⅱ(0.012 7 mg·L-1);给药2.5 h后,淫羊藿苷(0.134 3 mg·L-1)、淫羊藿次苷Ⅰ(0.080 4 mg·L-1)及淫羊藿次苷Ⅱ(0.102 4 mg·L-1)质量浓度均较高,24 h后基本消除;2.5 h检测到淫羊藿素(0.027 2 mg·L-1),4 h质量浓度较高(0.082 2 mg·L-1),24 h时仍存在(0.025 9 mg·L-1)。结论:淫羊藿苷在大鼠肾脏中分布较快,与其代谢产物共存于肾脏组织中,具有较高的质量浓度并能维持一定时间,提示其作用靶点可能为肾脏,与中医学理论认为淫羊藿归肝、肾经相符合。建立的HPLC简便、快速,为淫羊藿苷的体内研究提供参考。
Objective: To explore tissues distribution characteristics of icariin and its metabolites including icarisid Ⅰ, icarisid Ⅱ and icaritin in the kidney of osteoporosis model rats after intragastric administration of icariin. Method: Kidney tissues were gotten from rats in 40 min,1. 5,2. 5,4,12,24 h after intragastric administration of icariin with dosage of 118 mg·kg- 1. After pretreated biological samples,HPLC was employed to determine contents of icariin and its metabolites with mobile phase of 0. 4% aqueous acetic acid(A)-methanol(B) for gradient elution(0-11 min,43% A; 12-30 min,37% A; 31-46 min,43% A) and detection wavelength at 270 nm. Result: At 40 min after intragastric administration,icariin(0. 017 5 mg·L- 1),icarisid Ⅰ(0. 014 2 mg·L- 1) and icarisid Ⅱ(0.012 7 mg·L- 1) could be checked out; these ingredients reached high concentrations at 2. 5 h and eliminated basically after 24 h. Icaritin was checked out at 2. 5 h and arrived the high concentration at 4 h,but it still exited at 24 h. Conclusion: Icariin distributed fast and coexisted with its metabolites in the kidney of rats,these ingredients had higher concentrations and maintained a certain period of time in the kidney,which pointed their target may be the kidney,it matched the Chinese medicine theory that Epimedii Folium went through the liver and kidney. This established method was accurate and fast,which could provide a reference for in vivo pharmacokinetic research of icariin.
Objective: To explore tissues distribution characteristics of icariin and its metabolites including icarisid Ⅰ, icarisid Ⅱ and icaritin in the kidney of osteoporosis model rats after intragastric administration of icariin. Method: Kidney tissues were gotten from rats in 40 min,1. 5,2. 5,4,12,24 h after intragastric administration of icariin with dosage of 118 mg·kg- 1. After pretreated biological samples,HPLC was employed to determine contents of icariin and its metabolites with mobile phase of 0. 4% aqueous acetic acid(A)-methanol(B) for gradient elution(0-11 min,43% A; 12-30 min,37% A; 31-46 min,43% A) and detection wavelength at 270 nm. Result: At 40 min after intragastric administration,icariin(0. 017 5 mg·L- 1),icarisid Ⅰ(0. 014 2 mg·L- 1) and icarisid Ⅱ(0.012 7 mg·L- 1) could be checked out; these ingredients reached high concentrations at 2. 5 h and eliminated basically after 24 h. Icaritin was checked out at 2. 5 h and arrived the high concentration at 4 h,but it still exited at 24 h. Conclusion: Icariin distributed fast and coexisted with its metabolites in the kidney of rats,these ingredients had higher concentrations and maintained a certain period of time in the kidney,which pointed their target may be the kidney,it matched the Chinese medicine theory that Epimedii Folium went through the liver and kidney. This established method was accurate and fast,which could provide a reference for in vivo pharmacokinetic research of icariin.
引文
[1]国家药典委员会.中华人民共和国药典.一部[S].北京:中国医药科技出版社,2010:306.
[2]杜道兵,卢万根,曹丛仁,等.淫羊藿苷促进宫颈癌TC-1细胞凋亡作用的研究[J].现代生物医学进展,2011,11(4):646.
[3]龚其海,杨丹莉,石京山,等.淫羊藿苷的神经药理作用及分子机制研究进展[J].中国新药与临床杂志,2011,30(7):481.
[4]夏国莲,黄兆铨.淫羊藿对心血管系统药理作用的研究新进展[J].中华中医药学刊,2010,28(8):1676.
[5]刘波,张睿,徐彭,等.淫羊藿对去卵巢大鼠骨质疏松的影响[J].中国实验方剂学杂志,2013,19(7):178.
[6]贾晓斌,钱浅,孙娥,等.淫羊藿黄酮药代动力学研究进展[J].中成药,2012,34(11):2193.
[7]刘海培,孟繁华,郭继芬,等.高效液相色谱-串联质谱法测定大鼠血浆中淫羊藿素[J].药学学报,2009,44(10):1140.
[8]叶丽卡,陈济民,刘四海,等.淫羊藿苷在大鼠体内的药代动力学[J].临床药学,1999,34(1):33.
[9]刘子琛,徐英,陈世忠.淫羊藿次苷Ⅰ在大鼠体内的药动学和组织分布研究[J].中国药学杂志,2008,43(11):848.
[10]张依,姚志红,秦子飞,等.LC-MS/MS测定家兔胆汁中淫羊藿次苷II[J].暨南大学学报:自然科学版,2012,33(3):305.
[11]钟大放.以加权最小二乘法建立生物分析标准曲线的若干问题[J].药物分析杂志,1996,16(5):343.
[2]杜道兵,卢万根,曹丛仁,等.淫羊藿苷促进宫颈癌TC-1细胞凋亡作用的研究[J].现代生物医学进展,2011,11(4):646.
[3]龚其海,杨丹莉,石京山,等.淫羊藿苷的神经药理作用及分子机制研究进展[J].中国新药与临床杂志,2011,30(7):481.
[4]夏国莲,黄兆铨.淫羊藿对心血管系统药理作用的研究新进展[J].中华中医药学刊,2010,28(8):1676.
[5]刘波,张睿,徐彭,等.淫羊藿对去卵巢大鼠骨质疏松的影响[J].中国实验方剂学杂志,2013,19(7):178.
[6]贾晓斌,钱浅,孙娥,等.淫羊藿黄酮药代动力学研究进展[J].中成药,2012,34(11):2193.
[7]刘海培,孟繁华,郭继芬,等.高效液相色谱-串联质谱法测定大鼠血浆中淫羊藿素[J].药学学报,2009,44(10):1140.
[8]叶丽卡,陈济民,刘四海,等.淫羊藿苷在大鼠体内的药代动力学[J].临床药学,1999,34(1):33.
[9]刘子琛,徐英,陈世忠.淫羊藿次苷Ⅰ在大鼠体内的药动学和组织分布研究[J].中国药学杂志,2008,43(11):848.
[10]张依,姚志红,秦子飞,等.LC-MS/MS测定家兔胆汁中淫羊藿次苷II[J].暨南大学学报:自然科学版,2012,33(3):305.
[11]钟大放.以加权最小二乘法建立生物分析标准曲线的若干问题[J].药物分析杂志,1996,16(5):343.