阿米替林对脑缺血再灌注大鼠大脑皮质中氨基酸类神经递质的影响

 目的通过观察阿米替林对大鼠局灶性脑缺血再灌注大脑皮质氨基酸类神经递质的影响,探讨其对大鼠局灶性脑缺血-再灌注损伤的保护作用。方法SD大鼠随机分为假手术组,缺血再灌注模型组,阿米替林高、中、低剂量组及尼莫地平阳性对照组。术前采用腹腔注射给药,假手术组及缺血再灌注模型组给予等量的生理盐水。采用线栓法建立大鼠局灶性脑缺血再灌注损伤模型,用Longa法进行神经功能缺损评分;高效液相色谱法测定大鼠大脑皮质中谷氨酸(Glu)、天门冬氨酸(Asp)、甘氨酸(Gly)、γ-氨基丁酸(GABA)、牛磺酸(Tau)的含量,并计算兴奋毒性指数(EI)的变化。结果缺血1 h再灌注2 h后,与假手术组相比,缺血再灌注模型组大鼠神经功能缺损评分分值明显升高(P<0.01),大鼠大脑皮质中Glu、Asp、GABA、Gly、Tau的含量及EI值均显著增加(P<0.01或P<0.05);与缺血再灌注模型组相比,阿米替林组及尼莫地平组大鼠神经功能缺损评分分值显著降低(P<0.01),大鼠大脑皮质中Glu、Asp、Gly含量均明显降低,GABA、Tau有所增加,EI值明显降低(P<0.01或P<0.05)。结论阿米替林对局灶性脑缺血再灌注引起损伤的神经具有保护作用。其机制可能与其抑制兴奋性氨基酸的堆积,稳定兴奋性氨基酸/抑制性氨基酸递质的平衡有关。

Effects of Amitriptyline on Amino Acids in Ischemic Areas in Rats Subjected to Focal Cerebral Ischemia Reperfusion

OBJECTIVE To investigate the role of amitriptyline in the cerebral ischemia-reperfusion,by the determination of the content of Glu,Asp,Gly,GABA and Tau in the cerebral of rats after ischemia for 1 h and reperfusion for 2 h.METHODS The middle cerebral artery occlusion(MCAO)models were made using the suture emboli methods.The animals were divided into 6 groups with 8 animals in each group: sham group received operation without MCA occlusion and reperfusion,ischemia-reperfusion group received 1 h MCA occlusion followed by 2 h reperfusion without medication,the other groups received amitriptyline or nimodipine intraperitoneally before 1 h MCA occlusion followed by 2 h reperfusion.The neurofunctional behaviour was assessed by Longa' method.The contents of various amino acids in brain tissue were measured by high performance liquid chromatogram(HPLC).RESULTS The score values of neurofunctional behaviour were ascended in ischemia-reperfusion group compared with sham group,the score values in amitriptyline and nimodipine groups were descended compared with ischemia-reperfusion group.Amitriptyline and nimodipine significantly reduced Glu,Asp and Gly accumulation in ischemic areas during ischemia-reperfusion and values of EI,augmented the contents of GABA and Tau.CONCLUSION Amitriptyline has protective effects on cerebral ischemia-reperfusion injury in rats.The mechanism might be related to inhibiting the level of excitatory amino acid(Glu,Asp,Gly) and maintaining the balance of excitatory amino acid and inhibitory amino acid(GABA) when cerebrum of rats was ischemia-reperfusion.