低氧和氧化应激中NO介导培养神经元损伤机理的实验研究

Study of the mechanism of cultured neuron injury mediated by nitric oxide during hypoxia and oxidative stress

目的 探讨低氧、氧化应激中一氧化氮（ NO）和氧自由基之间关系及其对培养神经元的损伤机理。方法 对培养的新生大鼠神经细胞分别进行低氧、 H_2O_2氧化应激处理和超氧化物歧化酶（ SOD）抗氧化应激处理，用比色法等检测培养上清液中 NO、丙二醛（ MDA）、乳酸脱氢酶（ LDH）和 SOD含量变化指标。结果 与对照组比较，低氧组和 H_2O_2组的 NO、 LDH、 MDA含量均显著增高， SOD含量显著降低， NO与 SOD含量变化呈负相关关系。预先给予终浓度为 200U/ml的 SOD处理，可使神经细胞的 NO、 LDH和 MDA释放量明显减少。各组间 NO含量与 LDH、 MDA含量呈正相关关系。结论 低氧、氧化应激促使神经元 NO产生增多， NO有增加氧自由基对神经细胞的损伤作用。 SOD具有清除氧自由基和减轻 NO对神经元的损伤作用。

Objective To study the mechanisms of cultured neurons injury mediated by nitric oxide and free oxygen radicle during hypoxia and oxidative stress.Methods The cultured newborn rat neurons were treated with hypoxia, H_2O_2 and pretreated superoxide dismutase (SOD) respectively. We examined the content of NO, malonaldehyde (MDA), lactate dehydrogenase (LDH) and SOD in cultured supernatant.Results Comparing with that of control group, the content of NO, LDH, MDA increased and the content of SOD decreased in hypoxia group and H_2O_2 group. The content between NO and SOD showed the negative correlation. Administration of 200 U/ml SOD before oxidative stress could efficiently decrease the release of NO, LDH and MDA in neurons. The content of NO, LDH and MDA manifested in postive correlation in each group.Conclusion Hypoxia and oxidative stress increased NO production which strengthen neurons injury induced by free radicle. SOD played an important role in elimination of free oxygen radicals and protecting neurons from injury by NO. [