神经元缺氧复氧损伤时氧自由基的毒性作用及其机制

在原代分离培养Ｗｉｓｔａｒ乳鼠大脑皮质神经元上研究了缺氧复氧损伤（Ｈ／Ｒ）对神经细胞乳酸脱氢酶（ＬＤＨ），漏出率，死亡率和脂质过氧化物含量的影响，并选用一氧化氮（ＮＯ）合酶抑制剂Ｌ－ＮＧ－硝基－精氨酸（Ｌ－ＮＮＡ）巯基供体Ｎ－乙酰半胱氨酸（ＮＡＣ）和超氧化物歧化酶（Ｃｕ，Ｚｎ－ＳＯＤ）三种自由基清除剂进行预保护等方法来探讨机制。结果表明 Ｈ／Ｒ损伤引起ＬＤＨ漏出率，细胞死亡率和脂过氧化物含量极显著

THE STUDY ON OXYGEN FREE RADICAL TOXICITY AND ITS MECHANISM IN CULTURED RAT CEREBRAL CORTEX NEURON DAMAGED BY HYPOXIA AND REOXYGENATION

The effect of hypoxia/reoxygenation injury (H/R) on lactic dehydrogenase (LDH) leaking rate, cellular death rate,and the increase of lipid peroxide content were studied in cultured cerebral cortical neurons of infant wistar rat. Meanwhile it's mechanism was explored by pretreating with L-NNA, NAC and Cu, Zn-SOD. The results showed that H/R injury increased the above three indexes; and pretreatment with 1mmol/L NAC or 500U/ml SOD could inhibit them; on the contrary, pretreatment with 0.5mmol/L L-NNA had no significant inhibition effect. Neuronal LDH leaking rate induced by H/R and NO-donor SIN-1 injury was higher than H/R injury alone. In pure cultured neuron, the inhibitory effect of 0.5mmol/L L-NNA on theincrease of LDH leaking after exposure of H/R and SIN-1 had also no statistical significance, but it could inhibit significantly the above index in mixedly cultured cerebral cortex neuron and glia. Thus in H/R injury of cultured cerebral cortex cells, the oxidative injury of superoxide anion and other oxygen free radicals played an important role. In H/R injury of mixedly cultured cerebral cortex neuron and glia, the increase of NO production which was mainly generated by glia, participated in oxidative insult.