脑脊液中大分子物质经淋巴途径引流评估方法的建立  

A method to evaluate lymphatic drainage of macromolecular tracer in cerebrospinal fluid

作　　者：孙保亮[1] 贾莉[1] 孙田歌[1] 杨明峰[1] 袁慧[1] 王彦辉[2] 高允生[3] 

机构地区：[1]山东省高校脑微循环重点实验室,泰山医学院附属医院神经内科 [2]泰山医学院附属医院药剂科,山东泰安271000 [3]山东省高校药理学重点学科,泰山医学院药学院,山东泰安271016

出　　处：《中国药理学通报》2010年第1期132-134,共3页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No30570651,30670724,30770759);山东省教育厅科技计划资助项目(NoJ05L10);山东省中医药科技发展计划资助项目(No2005-231);山东省保健医学科研计划资助项目(No2005-1);山东省卫生系统高层次人才基金资助项目

摘　　要：目的探讨大鼠脑脊液(CSF)中大分子物质经淋巴途径引流的评估方法。方法采用颈淋巴管结扎和颈淋巴结摘除法制作大鼠颈部淋巴引流阻断(CLB)模型,将动物分为非CLB组和CLB组。将125I标记的人血清白蛋白(125I-HSA,CSF示踪剂)注入大鼠左侧脑室,在24h内连续取动脉血样,并检测血浆中CSF示踪剂125I-HSA的浓度。根据药代动力学一室模型的基本原理,绘制浓度-时间曲线,计算出125I-HSA从CSF转运至血浆的浓度-时间曲线下面积(AUC)、血浆中125I-HSA的最大浓度(Cmax)、转运速率常数(Ka)、浓度达峰时间(Tmax)等药代动力学参数,根据两组的差值推算出大鼠CSF示踪剂经淋巴引流途径清除的AUC、Cmax、Ka和Tmax。结果大鼠CSF示踪剂125I-HSA经淋巴引流途径清除的AUC、Cmax、Ka分别为51.97mg·L-1·h-1、2.91mg·L-1、0.64h-1,分别占经蛛网膜绒毛和淋巴引流两条途径清除的AUC、Cmax、Ka的71.53%、44.02%、58.18%。CLB组Tmax(8.36±0.82)h长于非CLB组(3.57±0.54)h。结论成功建立了大鼠CSF中大分子物质经淋巴途径引流的评估方法,经淋巴途径的引流在大鼠CSF大分子物质清除中具有重要作用。Aim To establish a method to evaluate lymphatic drainage of macromolecular tracer in cerebrospinal fluid in rats. Methods Rat cervical lymphatic blockade（CLB） models were established by occlusion of cervical lymphatic tubes and removal of cervical lymphatic nodes. The rats were divided into non CLB （normal controls） and CLB groups. 125I-labeled human serum albumin（125I-HSA）was injected into the left lateral cerebral ventricle,and blood samples were collected and 125I-HSA concentrations were detected continually within 24 hours. Concentration-time curve was drawn according to the single compartment model in pharmacokinetics. Parameters of pharmacokinetics such as area under curve（AUC）,maximum concentration（Cmax）,transfer rate constant Ka and peak time（Tmax） were derived. The AUC, Cmax,Ka,and Tmax regarding the lymphatic drainage of 125 I-HSA were calculated based on the differences between the two groups.Results AUC,Cmax,Ka of ^125I-HSA by lymphatic drainage were 51.97mg·L^-1·h^-1,2. 91 mg·L^-1,and 0.64 h-1,respectively. The proportion of AUC,Cmax,Ka of 125 I-HSA by lymphatic drainage to those of drained by both arachnoid granulations and lymphatics was 71. 53% ,44. 02% ,58. 18% ,respectively. Tmax in CLB group（8.36±0.82 h） was much longer than that in non CLB group（3.57±0.54 h）. Conclusions A method to evaluate lymphatic drainage of macromolecular tracer in cerebrospinal fluid in rats is successfully established. The lymphatic drainage pathway plays an important role in eliminating macromolecular substances in cerebrospinal fluid.

关 键 词：脑脊液 大分子物质 引流 淋巴 蛛网膜绒毛 大鼠 

分 类 号：R-332[医药卫生] R331.37