摘要
目的:观察清热解毒活血中药有效组分配伍通络清脑注射液对脑缺血再灌注损伤大鼠脑微透析液中2种氨基酸类神经递质谷氨酸(Glu)和γ-氨基丁酸(gamma-aminobutyric acid,GABA)水平的影响。方法:24只SD大鼠随机分为大脑中动脉阻塞/再灌注(MCAO/RP)模型组,尼莫地平组(0.4 mg·kg-1),通络清脑注射液低剂量组(48 mg·kg-1)及高剂量组(95mg·kg-1),每组6只。采用微透析技术对大鼠纹状体脑组织进行连续取样,流速1μL·min-1,每30 min采集1个样品。收集至第3个样品时,采用线栓法制备MCAO/RP模型,90 min后拔出线栓,实现再灌注,同时经大鼠尾静脉给予各组药物,继续收集微透析液至再灌注后180 min。微透析液样品经柱前衍生化后,经高效液相色谱-电化学(HPLC-ECD)检测Glu和GABA的水平。分别以造模时间点Glu及GABA含量为基础值计算释放率百分比。结果:建立MCAO模型后,各组Glu,GABA释放量均急剧上升,造模后120 min,通络清脑注射液高剂量组Glu释放量(327.29±127.31)%与模型组(1 041.08±190.57)%相比明显下降(P<0.05),造模后120,150 min,通络清脑注射液高剂量组GABA释放量(11 843.99±3 952.45)%,(4 785.80±3 051.98)%与模型组(35 204.61±6 919.45)%,(27 694.76±18 393.61)%相比明显下降(P<0.05)。随后各组Glu,GABA释放量均呈逐渐下降趋势。结论:抑制氨基酸的过量释放是通络清脑注射液抗脑缺血/再灌注损伤的可能机制之一。
Objective： To investigate the effect of Tongluo Qingnao injection on the levels of two aminoacid neurotransmitters, glutamate （Glu） and gamma-aminobutyric acid （GABA）, in cerebral microdialysis samples of ischemia/reperfusion rats. Method： 24 Sprague-Dawley rats were randomly divided into 4 groups with 6 in each group, the middle cerebral artery occlusion/reperfusion （MCAO/RP） model group, the nimodipine （0.4 mg· kg-1） group, low-dose （48 mg ·kg-1） group and high-dose （95 mg·kg-1） group of Tongluo Qingnao injection. Continuous cerebral microdialysis samples were acquired from the rat striatum, and the flow rate was 1 μL .min-1, each every 30 min. After 2 samples were collected, the MCAO model was established. After 90 min, the suture was removed and drugs of each group were administrated by caudal vein while reperfusion. The collection was ended 180 min after reperfusion. Glu and GABA in dialysate were pre-column derivatived and their levels were detected by an HPLC-ECD system. Result： The emission content of Glu and GABA was standardized based on data of model group. After modeling, there was a steep rise of Glu and GABA level in all groups. The emission content of Glu was significantly decreased in the Tongluo Qingnao high-dose group （327.29 ± 127.31）% compared to the model group （ 1 041.08 ± 190. 57） % （P 〈 0. 05） 120 min after modeling, and the emission content of GABA was significantly decreased in the Tongluo Qingnao high-dose group （11 843.99 ± 3952.45）%, （4 785.80 ± 3 051.98） % compared to the model group （35 204. 61 ± 6 919.45） %, （27 694. 76 ± 18 393.61 ） % （ P 〈 0. 05 ） 120 min and 150 min after modeling, respectively. Conclusion： Tongluo Qingnao injection probably plays the neuro-protective role by inhibiting the excessive release of amino acids.
出处
《中国实验方剂学杂志》
CAS
北大核心
2014年第12期136-140,共5页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金项目(30772755)
国家科技部“十一五”重大新药创制课题(2009ZX09013-317)
国家科技部“十二五”重大新药创制课题(2012ZX09101214)
