生地低聚糖微粉中水苏糖在大鼠体内的组织分布研究  

Tissues Distribution of Stachyose in Micronised Rehmanniae Radix Oligosaccharide in Rats

作　　者：周扬[1,2] 刘力[1,2] 徐德生[1,2] 裘福荣[1,2] 徐光临[1] 许希宁 罗会龙[2] 张志荣[1,2] ZHOU Yang LIU Li XU Desheng QIU Furong XU Guanglin XU Xining LUO Huilong ZHANG Zhirong(Shuguang Hospital Affiliated To Shanghai University of Traditional Chinese Medicine, Shanghai 200021, China Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China)

机构地区：[1]上海中医药大学附属曙光医院,上海200021 [2]上海中医药大学,上海201203

出　　处：《中国现代应用药学》2016年第11期1422-1428,共7页Chinese Journal of Modern Applied Pharmacy

基　　金：上海市科技计划基金项目(05dz19102)

摘　　要：目的研究生地低聚糖微粉中水苏糖在大鼠体内的组织分布特点。方法选取健康SD大鼠,♂,肺部给药生地低聚糖微粉100 mg·kg^(-1),并于给药后0.25,0.5,1,3,5,8和12 h共7个时间点各处死1组大鼠,取肝、肾和肺,采用HPLC-MS/MS测定各组织中水苏糖的浓度。色谱条件:采用Shodex Asahipak NH2P-50 4E色谱柱(250 mm×4.6 mm,5μm)和Asahipak NH2P-50G 4A保护柱(10 mm×4.6 mm),柱温为25℃,流动相为乙腈-水(55∶45),体积流量1.0 m L·min^(-1),进样量为1μL。质谱采用电喷雾离子源(ESI),负离子模式,离子源温度为450℃,扫描方式为多反应监测(MRM),用于检测的离子对分别为m/z[M-H]-665.4→383.1(水苏糖)和665.5→485.0(蔗果四糖,内标)。结果水苏糖在大鼠肺部的浓度最高,肝中最少。肺部给药15 min后水苏糖在各组织中浓度度均达到最高,其中在肝中为(43.20±5.60)μg·m L^(-1),肾中为(130.80±7.01)μg·m L^(-1),肺中为(1 112.00±98.54)μg·m L^(-1),随后逐渐降低,而在5 h时肾组织中水苏糖浓度又有升高的趋势,之后继续下降。结论水苏糖在体内消除较快。水苏糖的组织分布特征可为生地低聚糖微粉的进一步研究开发、药效研究和临床应用提供参考依据。OBJECTIVE To study the tissues distribution characteristics of stachyose in rats after pulmonary delivery of micronized Rehmanniae Radix oligosaccharide（RGOS）. METHODS A single dose of 100 mg·kg（-1） micronized RGOS was given to healthy SD male rats via pulmonary administration. The tissues of liver, kidney and lung were acquired at 0.25, 0.5, 1, 3, 5, 8 and 12 h after administration. The concentrations of stachyose in tissue samples were determined by LC-MS/MS on an Asahipak NH2P-50 4E column（250 mm×4.6 mm, 5 μm） with an Asahipak NH2P-50 G 4A guard column（10 mm×4.6 mm）, and the column temperature was kept at 25 ℃ The mobile phase consisted of acetonitrile and water（55∶45） at a flow rate of 1 m L·min（-1）. The auto-sampler was conditioned at 4 ℃ and the sample injection volume was 1 μL. Detection and quantification were conducted by LC-MS/MS method in the negative ion mode using multiple reaction monitoring（MRM） transitions at m/z [M-H]- 665.4→383.1 for stachyose and 665.5→485.0 for IS, respectively. RESULTS After pulmonary administration of 100 mg·kg（-1） micronized RGOS in rats, stachyose was mainly distributed in kidney. The concentrations of stachyose in liver was low. The concentrations of the tissues at 15 min after pulmonary administration all reached the highest, in which the liver occupied（43.20±5.60）μg·m L（-1）, kidney occupied（130.80±7.01）μg·m L（-1） and lung（1 112.00±98.54）μg·m L（-1）, then the concentrations decreased gradually, but the concentration of stachyose in kidney tissue increased after 5 h and then decreased continually. CONCLUSION The in vivo eliminatiion of stachyose is fast. The present investigation on stachyose tissues distribution can provide information for the further study and clinic use of micronized RGOS.

关 键 词：水苏糖 肺部给药 生地低聚糖微粉 LC-MS/MS 组织分布 

分 类 号：R979.1[医药卫生—药品]