人参皂苷Rg1神经保护作用及脑部转运的研究(英文)  

Neuroprotective Effects and Brain Transport of Ginsenoside Rg1

作　　者：王睿[1] 李燕楠[1] 王广基[1] 郝海平[1] 吴晓兰[1] 周芳[1] 

机构地区：[1]中国药科大学药物代谢动力学重点实验室,南京210009

出　　处：《中国天然药物》2009年第4期315-320,共6页

基　　金：supported by the National Naural Science Foundation of China (No. 30630076)~~

摘　　要：目的:人参皂苷Rg1是人参的主要成分之一,现代药理学研究证明其有中枢神经系统的保护作用。然而,人参皂苷Rg1能否有效地透过血脑屏障发挥中枢神经系统保护作用并不清楚。本研究旨在于研究人参皂苷Rg1在正常及脑缺血/再灌注病理情况下透血脑屏障的特性,初步探讨其中枢神经系统保护作用的潜在靶点。方法:整体动物采用大鼠脑中动脉短暂性闭塞造脑缺血/再灌注模型,通过脑梗死体积与神经学评分观察Rg1中枢神经系统的保护作用。同时于体内外实验中观察Rg1透血脑屏障的特性。结果:人参皂苷Rg1可显著地减小病理状态下大鼠脑梗死体积与神经学评分。而整体动物脑组织样品中并未检测到Rg1(最低定量浓度2.5ng·mL-1)。于体外实验中观察到,病理状态下Rg1透血脑屏障的量略有增加,但统计学差异无显著性意义,体内外结果提示Rg1透血脑屏障的能力很弱。体外实验中,Rg1可保护脑微血管内皮细胞,提高其病理状态下的存活率。结论:人参皂苷Rg1透血脑屏障的能力很弱,其确切的抗脑缺血/再灌注保护作用可能来源于其对血脑屏障的保护作用。AIM： Ginsenoside Rgl, one of the major ingredients of Panax notoginseng saponins （PNS）, has been proven to possess protective effects on the central nerve system （CNS）. However, whether ginsenoside Rgl could efficiently be transported through the blood brain barrier to elicit its neuroprotective effects remains still unclear. The present study was thus aimed to characterize its transport properties through BBB under normal and ischemia/reperfusion damaged conditions, and to disclose the potential pharmacological target. METHODS： Rgl brain transport was conducted in the normal and middle cerebral artery occlusion rats, and in an in vitro BBB transport model. Neurological scores and infarct volume were determined to confirm its neuroprotective effects. RESULTS： Ginsenoside Rg1 showed a potent neuroprotective effect by remarkably decreasing the brain infarct volume and neurological scores in the MCAO rat models. The transport capacity of ginsenoside through the blood brain barrier was quite limited since it failed to be detected in the brain tissue of both normal and MCAO rats. Although its transport through the hydrogen peroxide induced BBB damaged model in vitro was slightly enhanced, the results obtained from this study indicated that the BBB permeability of ginsenoside Rgl was very poor. In contrast, ginsenoside Rg1 exhibited a potent protective effect against BBB damage as evidenced from the increased TEER, decreased marker compound permeability and the MTT test. CONCLUSION： Ginsenoside Rg1 transport through the BBB is very poor and its neuroprotective effect may derive from its direct protective effect against ischemia caused by BBB damage and BBB might be its primary target.

关 键 词：人参皂苷RG1 脑缺血/再灌注 血脑屏障 转运 

分 类 号：R969.1[医药卫生—药理学]