L-精氨酸对局灶性脑缺血大鼠脑组织氨基酸含量的影响

Effects of L-arginine on amino acid contents of ischemic brain in rats

目的观察L-精氨酸对脑缺血大鼠纹状体、海马、皮层中天门冬氨酸(Asp)、谷氨酸(Glu)、甘氨酸(Gly)、γ-氨基丁酸(GABA)含量的影响,探讨L-精氨酸对大鼠脑缺血组织的保护作用及其作用机制。方法采用线栓法复制大鼠中脑动脉梗塞(MCAO)模型,缺血后给予L-精氨酸治疗。相应时间断头取脑,然后测定脑梗死体积、脑组织中氨基酸的含量。结果L-精氨酸组脑梗死体积较缺血组明显缩小;与假手术组比较,缺血组纹状体、海马、皮层中Asp、Glu、Gly、GABA含量显著增加,给予L-精氨酸治疗后,缺血后2、6h治疗组Asp、Glu的含量明显降低,Gly、GABA含量明显升高。结论L-精氨酸降低脑组织中兴奋性氨基酸的含量及升高抑制性氨基酸的含量可能是保护脑缺血的重要机制。

Objective By evaluating the effect of nitric oxide （NO） donor L-arginine on the contents of aspartate,glutamate, glycine and γ-aminobutyric acid （GABA） in striatum, hippocampus and cortex in the rat brain following cerebral ischemia respectively, to investigate the beneficial effect of L-arginine on cerebral ischemic injury and the possible mechanism.Methods The model of focal cerebral ischemia in rat was prepared. Rats were divided into sham-operated group, ischemic group and L-arginine treatment group. Each group was further divided into 3 subgroup （ n = 6 for each）： drugs were administrated at 2, 6 and 12 h after the middle cerebral artery occlusion （MCAO） respectively. L-arginine （500 mg/kg, ip） was administrated, 2 times a day, for 3 consecutive days. The changes of infarct volume and the contents of amino acids were assayed. Results The infarct volume （IV%） was not significantly different from the ischemic group in L-arginine group administrated at 12 h after MCAO, and was markedly decreased compared with that of ischemic group when L-arginine was administrated at 2 or 6 h after MCAO（ P 〈 0.05, n = 6） respectively. The contents of aspartate, glutamate, glycine and GABA in striatum, hippocampus and cortex in ischemic group were significantly increased compared with sham-operated group （ P 〈 0.05 or P 〈 0.01, n = 6）. The contents of aspartate, glutamate, glycine and GABA in striatum, hippocampus and cortex were not significantly different from the ischemic group in L-arginine group administrated at 12 h after MCAO respectively. The contents of aspartate and glutamate was markedly decreased compared with that of ischemic group, but the contents of GABA and glycine in hippocampus were higher than those of ischemic group when L-arginine was administrated at 2,6 h after MCAO（ P 〈 0.05, n = 6）. Conclusion It could be concluded that L-arginine have beneficial effect on ischemic cerebral injury in ischemic early stage in rats. The possible mechanism is that L-arginine can decrease the contents of aspartate and glutamate, increase the contents of glycine and GABA.