松果菊苷对脑缺血大鼠纹状体细胞外液中氨基酸水平的影响

Effects of echinacoside on striatal extracellular levels of amino acid neurotransmitter in cerebral ischemia rats

目的研究松果菊苷(ECH)对急性脑缺血大鼠纹状体细胞外液中4种氨基酸水平和脑梗死率的影响,以探讨ECH对脑神经保护作用的可能机制。方法 SD大鼠随机分为假手术对照组、模型组、阳性药川芎嗪组(CXQ,40 mg.kg-1)、ECH高剂量(ECH 40 mg.kg-1)组、ECH低剂量(ECH 20mg.kg-1)组和ECH配伍冰片(ECH 40 mg.kg-1,冰片400mg.kg-1)组。各组大鼠给予相应的药物或者生理盐水腹腔注射,每天1次,连续7 d。在给药d 3,脑纹状体埋置探针套管,末次给药1 h后,制作大鼠局灶性脑缺血模型(MCAO),模型成功后立刻进行微透析。将透析液注入高效液相-荧光检测器(HPLC-RF),此方法较氨基酸分析仪相比较,具有最低检测限低等特点,检测各组纹状体细胞外液中天门冬氨酸(Asp)、谷氨酸(Glu)、甘氨酸(Gly)、γ-氨基丁酸(GABA)的含量。结果与假手术对照组相比,模型组的Asp、Glu、Gly、GABA水平均明显升高;ECH给药组与模型组相比,ECH高剂量组能明显降低Asp、Glu的水平,而ECH低剂量组与ECH配伍冰片组Asp、Glu降低均不明显;ECH高、低组与配伍冰片组对Gly、GABA的影响均不明显;与模型组相比,ECH高、低剂量组能明显地缩小脑梗死面积。结论 ECH对脑神经的保护作用可能与对抗脑缺血后兴奋性氨基酸升高有关。

Aim To examine the effects of echinacoside（ECH） on striatal extracellular levels of ASP,Glu,Gly,GABA in cerebral ischemia rats and the rate of cerebral infarction and explore its possible mechanisms of neuro-protective effect.Methods SD rats were divided into sham,model,positive control drug（CXQ 40 mg·kg-1）ECH high（ECH 40 mg·kg-1） and low dose（ECH 20 mg·kg-1）and HB groups（ECH 40 mg·kg-1,Borneo camphor 400 mg·kg-1） randomly.Every rat was administered drugs or vehicle through intraperitoneal injection,once a day for seven days.At the third day of administration,the probe tube was embedded in the striatum.1 h after the last administration,focal ischemia was generated by permanent middle cerebral artery occlusion（MCAO）.Then the striatal extracellular fluids were gained by brain microdialysis.The methods of high performance liquid chromatography with fluorescence detector were used to measure the striatal extracellular levels of Asp,Glu,Gly,and GABA.Results Compared with the sham group,the levels of Asp,Glu,Gly,GABA were elevated.Compared with model group,ECH high dose group decreased the levels of Asp,Glu;effects on Gly and GABA of ECH low dose and ECH HB group were not obvious in statistics.Compared with model group,ECH high dose and ECH low dose groups significantly reduced the infarct area.Conclusion ECH can reduce excitatory amino acids neurotransmitters of striatal extracellular levels,which may be one of the mechanisms of anti-cerebral ischemia.