垂体腺苷酸环化酶激活肽减轻一氧化氮介导的谷氨酸神经毒作用

Pituitary adenylate cyclase activating polypeptide attenuates the neurotoxicity mediated by nitric oxide

研究垂体腺苷酸环化酶激活肽 ( PACAP)是否通过作用于一氧化氮 ( NO)代谢途径 ,减轻谷氨酸的神经毒作用。取新生 SD大鼠海马 ,用 B2 7无血清培养基培养神经元 ;重氮化反应法测定 NO浓度 ,MTT法测定神经元存活率 ,PACAP能减少谷氨酸引起的海马神经元死亡 ;谷氨酸呈剂量依赖性地增加海马神经元培养液中 NO的含量 ,PACAP能不同程度地减少 NO的含量 ;分别给予 2 mmol/L L - Arg,1 0 0μmol/L SNP和 2 0 0 μmol/L SNAP处理后 ,海马神经元存活率明显下降 ,给予不同浓度的 PACAP( 1 0 -9,1 0 -11,1 0 -13mol/L)能增加神经元的存活率。上述结果提示 ,PACAP通过抑制 NO释放及其神经毒作用 ,减轻谷氨酸引起的海马神经元损害。

In this study,we aim to investigate whether pituitary adenylate cyclase activating polypeptide(PACAP) attenuated the neurotoxicity induced by glutamate through blocking the nitric oxide (NO) pathway.Hippocampus was isolated from new born SD rats and dispersedly cultured in the B27 medium.NO contents were determined by Diazotization assay and neuronal survival was measured by MTT assay.PACAP could decrease cultured hippocampal neuronal death induced by glutamate.Glutamate could dose dependently increase the release of NO in cultured hippocampal neurons.PACAP could inhibit the glutamate effect.Exposed to 2 mmol/L L Arg,100 μmol/L SNP and 200 μmol/L SNAP respectively,hippocampal neuronal survival greatly decreased.PACAP could significantly increase the neuronal survival in the concentration of 10 -9 ,10 -11 and 10 -13 mol/L.The results suggested that PACAP could ameliorate glutamate neurotoxicity via inhibiting the release of NO and protecting neurons against NO neurotoxicity. [