红毛五加多糖Ⅲ的荧光标记及其在小鼠体内的药动学研究  

Fluorescent labeling of Acanthopanax giraldii Harms polysaccharide and its pharmacokinetics in mice

作　　者：吴疆 郭晓晓 李儒月 贾明珠 李艳艳[2] 陈永[1] WU Jiang;GUO Xiao-xiao;LI Ru-yue;JIA Ming-zhu;LI Yan-yan;CHEN Yong(School of Basic Medicine,Weifang Medical University,Weifang Shangdong 261053;School of Life Science and Technology,Weifang Medical University,Weifang Shangdong 261053)

机构地区：[1]潍坊医学院基础学院,山东潍坊261053 [2]潍坊医学院生命科学与技术学院,山东潍坊261053

出　　处：《中南药学》2020年第8期1328-1333,共6页Central South Pharmacy

基　　金：国家自然科学基金(No.81303198);山东省大学生创新创业训练计划(No.KX2017006)。

摘　　要：目的对红毛五加多糖Ⅲ(AHP-Ⅲ)的还原性末端进行选择性荧光标记,并研究AHP-Ⅲ在小鼠体内的药动学特征。方法利用胺化还原法对AHP-Ⅲ进行异硫氰酸荧光素(FITC)荧光标记,并通过荧光分光光度计和紫外可见光谱扫描对偶联标记结果进行确证。通过小鼠单次静脉注射给予FITC-AHP-Ⅲ(f-AHP-Ⅲ)后,检测不同时间点样品中的荧光强度,用DAS软件求算药动学参数并分析。结果AHP-Ⅲ荧光标记后,多糖得率和荧光标记效率分别为36.43%和0.48%。血清、尿液等样品中f-AHP-Ⅲ的线性范围为3.75~120μg·mL-1(R2>0.9982),日内和日间RSD值≤11.13%,相对回收率在84.20%~106.94%。单次静脉注射给药后,主要动力学参数为:Cmax为(43.01±0.80)mg·L-1,tmax为0.08 h,AUC0~t为(113.87±1.30)mg·h·L-1,AUC0~∞为(148.35±2.27)mg·h·L-1,t1/2为(23.66±1.32)h,CLz为0.27 L/(h·kg),MRT为(29.75±1.63)h,Vz为(9.20±0.39)L·kg-1。组织中药物含量检测显示,单次静脉给药后f-AHP-Ⅲ在小鼠体内主要分布在肾、小肠、肺及肝脏等组织中,其排泄主要是以尿液的形式。结论成功实现了AHP-Ⅲ的荧光标记,绝大多数药物聚集在肾、小肠、肺及肝脏。上述研究为进一步阐明AHP-Ⅲ药理作用机制奠定了基础。Objective To fluorescent label Acanthopanax giraldii Harms polysaccharide Ⅲ (AHP-Ⅲ) selectively and confirm the pharmacokinetic characteristics of AHP-Ⅲ in mice.Methods Amination reduction method was used to fluorescent label AHP-Ⅲ.Fluorospectrophotometry and UV-Vis spectra were used to confirm the results.The fluorescence intensity of the samples at different time points was measured,and the pharmacokinetic parameters were calculated by DAS software after a single intravenous injection of f-AHP-Ⅲ.Results The yield of AHP-Ⅲ-FITC and the fluorescent substitute ratio were 36.43% and 0.48%,respectively.The regression linearity was 3.75-120 μg·mL-1 in the mice plasma,urine and other samples (R2>0.9982).The inter and intra-day precisions of the method were no higher than 11.13%,and the relative recovery was 84.20%- 106.94%.After intravenous injection,the pharmacokinetic parameters were as following:Cmax (43.01±0.80) mg·L-1,tmax 0.08 h,AUC0~t (113.87±1.30) mg·h·L-1,AUC0~∞ (148.35±2.27) mg·h·L-1,t1/2 (23.66±1.32) h,CLz 0.27 L/ (h·kg),and MRT (29.75±1.63) h,Vz (9.20±0.39) L·kg-1.The results indicated that f-AHP-Ⅲ was mainly distributed in the kidneys,intestine,lung and liver tissues in mice after the single intravenous injection.Its excretion was mainly in the form of urine.Conclusion The method can be used for the fluorescent labeling of AHP-Ⅲ.AHP-Ⅲ is mainly distributed in the kidney,intestine,lung and liver tissues.This research helps further elucidate the pharmacological mechanism of AHP-Ⅲ.

关 键 词：AHP-Ⅲ 荧光标记 小鼠 药动学 

分 类 号：R285.5[医药卫生—中药学]