L-硝基精氨酸对局灶性脑缺血大鼠脑组织氨基酸含量的影响

Effect of N^G-nitro-L-arginine on amino acid contents of ischemic brain in rat

目的:观察一氧化氮合酶(NOS)抑制剂L-硝基精氨酸(L-NA)对脑缺血大鼠纹状体、海马、皮质中天冬氨酸、谷氨酸、甘氨酸、γ-氨基丁酸(GABA)含量的影响,探讨L-NA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大脑中动脉梗塞(MCAO)模型,缺血后给予L-NA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:脑梗死体积L-NA组较缺血组明显缩小;与假手术组比较,缺血组大鼠纹状体、海马、皮质中天冬氨酸、谷氨酸、甘氨酸、GABA含量显著增加,给予L-NA治疗后,缺血后12 h治疗组中天冬氨酸、谷氨酸的含量明显降低,甘氨酸、GABA含量明显升高。结论:L-NA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： To investigate the beneficial effect of N^G -nitro-L-argmlne （L-NA） on cerebral ischemic injury and the possible mechanism by evaluating the effect of nitric oxide synthase （NOS） inhibitor,L-NA, on the contents of aspartate, glutamate, glycine andγ-aminobutyric acid （GABA） , respectively, in striatum, hippocampus and cortex of rat brain following cerebral ischemia. Methods：The model of focal cerebral ischemia in rat was prepared. Rats were divided into sham-operated group, ischemic group and L-NA group. Each group was further divided into 3 subgroup （n =6 for each） ： the middle cerebral artery occlusion （MCAO） was maintained for 2, 6 and 12 h, respectively. L-NA （20 mg/kg, ip） was administrated after MCAO, two times a day, for 3 consecutive days. The changes of infarcted volume and the contents of amino acids were assayed. Results ： The infarcted volume （ Ⅳ% ） was not significantly different among the ischemic groups with or without L-NA administrated 2 or 6 h after MCAO; and was markedly decreased in the ischemic group with L-NA administrated 12 h after MCAO （P 〈 0.05,n = 6）. 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, hippoeampus and cortex were not significantly different among the ischemic groups with or without L-NA group administrated 2 or 6 h after MCAO. The contents of aspartate and glutamate was markedly decreased, but the contents of GABA and glycine in hippocampus were increased in the ischemic group with L-NA administrated 12 h after MCAO （P 〈 0.05,n = 6 ）. Conclusion：It could be concluded that L-NA have beneficial effects on later stage ischemic cerebral injury in rats. The possible mechanism is that L-NA can decrease the contents of aspartate and glutamate, increase the contents of glycine and GABA.