摘要
目的探讨鞘内注射不同剂量人参皂苷Rg1对关节炎慢性吗啡耐受大鼠行为学和脊髓背角兴奋性氨基酸转运体1(excitatory amino-acid transporter1,EAAT1)即谷氨酸/天冬氨酸转运体(glutamate-aspar-tate transporter,GLAST)表达的影响,进以探讨人参皂苷Rg1对吗啡耐受影响的机制。方法鞘内置管成功并制成佐剂性关节炎模型的健康雄性SD大鼠36只,随机分为6组(n=6),分别经鞘内给予生理盐水10μL(NS组),吗啡10μg(M组),吗啡10μg加人参皂苷Rg150μg(MG50组)、100μg(MG100组)、200μg(MG200组)和单独人参皂苷Rg1100μg(G100组),鞘内注射生理盐水和吗啡每日2次,不同剂量人参皂苷Rg1每日1次,连续7天。动态检测各组大鼠50%机械缩爪阈值(paw withdrawal threshold,PWT),给药后第7天处死大鼠,取脊髓L3～L5节段,以免疫荧光方法检测大鼠脊髓背角GLAST表达水平。结果 M组在给药后第1、3天PWT显著高于NS组(P<0.05),随着用药天数增加,M组PWT逐渐缩短,到第7天与NS组差异无统计学意义(P>0.05),标志吗啡耐受的形成。MG100组PWT也呈下降趋势,但明显缓于M组(P<0.05)。G100组PWT高于NS组(P<0.05)。与NS组相比,M组脊髓背角GLAST表达下调(P<0.01),与M组比较,MG100组和G100组脊髓背角GLAST表达上调(P<0.05)。结论关节炎大鼠单独应用人参皂苷Rg1有轻微的镇痛作用,鞘内给予人参皂苷Rg1100μg有延缓吗啡耐受形成的作用,其机制可能与上调GLAST表达水平有关。
Objective To investigate the effects of intrathecal injection of ginsenoside Rg1 at different doses on the changes of the behavior and the expressions of excitatory amino-acid transporter 1 （EAAT1）, i.e., glutamate-aspartate transporter （GLAST） in the spinal dorsal horn of the arthritis rats with chronic morphine tolerance, and further to explore its mechanisms for morphine tolerance. Methods After successful intrathecal injection, an adjuvant arthritis model was established in 36 healthy male SD rats. They were randomly divided into 6 groups, 6 in each group. They were intrathecally injected with 10 μL normal saline （Group NS）, 10 μg morphine （Group M）, 10 μg morphine＋50 μg ginsenoside Rg1 （Group MG50）, 10 μg morphine ＋100 μg ginsenoside Rg1 （Group MG100）, 10 μg morphine＋200 μg ginsenoside Rg1 （Group MG200）, and 100 μg ginsenoside Rg1 （Group G100）, respectively. The normal saline and morphine were intrathecally injected twice daily, while ginsenoside Rg1 at different doses was intrathecally injected once daily, for 7 successive days. Fifty percent mechanical paw withdrawal threshold （PWT） was dynamically detected to evaluate their behaviors. The rats were sacrificed on day 7 after medication. The L3-L 5 segment of the spinal cord was isolated for determining the expression of GLAST in the spinal dorsal horn using immunofluorescence staining. Results The PWT of Group M was significantly higher than that of Group NS on the 1st and 3rd day after medication （P0.05）. But it was gradually shortened along with the increasing days of medication. There was no statistical difference between Group M and Group NS on the 7th day （P0.05）, indicating the formation of morphine tolerance. The PWT of Group MG100 also showed a decreasing tendency, but obviously slower than that of Group M （P0.05）. The PWT of Group G100 was higher than that of Group NS （P0.05）. Compared with Group NS, the expression of GLAST in the spinal dorsal horn of rats in Group M was down-regulated （P0.01）. Compared with Group M, the expression of GLAST in the spinal dorsal horn of rats in Group MG100 and Group G100 was up-regulated （P0.05）. Conclusions Single application of ginsenoside Rg1 showed mild antinociceptive effect in adjuvant-induced arthritis rats. Intrathecal injection of 100 μg ginsenoside Rg1 could attenuate the formation of morphine tolerance. Its mechanisms might be correlated with up-regulating of the expression of GLAST.
出处
《中国中西医结合杂志》
CAS
CSCD
北大核心
2012年第11期1539-1542,共4页
Chinese Journal of Integrated Traditional and Western Medicine
基金
天津市自然科学基金资助项目(No.06YFJMJC08600)
