9-(4-乙氧羰基苯氧基)-6,7-二甲氧基-1,2,3,4-四氢吖啶盐酸盐抑制自由基诱发鼠皮层神经元毒性及脑缺血损伤

目的考察9-(4-乙氧羰基苯氧基)-6,7-二甲氧基-1,2,3,4-四氢吖啶盐酸盐(EDT)对自由基致原代培养大鼠皮层神经毒及小鼠脑缺血损伤的影响。方法原代培养的鼠皮层神经细胞,用H₂O₂致自由基损伤模型,测定细胞内丙二醛(MDA)及超氧化物歧化酶(SOD)活性。结扎单侧颈总动脉及迷走神经造成小鼠慢性脑缺血模型,用跳台法研究EDT对记忆障碍的影响。同时,检测了大脑皮层形态学变化,脑匀浆内MDA,NO含量及SOD活力。结果在原代培养神经元,0.01～3 μmol·L^-1 EDT浓度依赖地抑制H₂O₂诱发的MDA生成及SOD活力降低。在小鼠脑缺血模型,EDT 2.5,5和10 mg·kg^-1 ig 5 d可显著改善脑缺血小鼠的记忆障碍,对抗脑内NO释放及MDA生成,增加SOD活力。结论EDT能有效对抗自由基诱发的神经元毒性及脑缺血损伤。

9-(4-Ethoxycarbonylphenoxy)-6,7-dimethoxy-1,2,3,4-tetrahydro acridine inhibits free radical induced rat cortical neuron cytotoxicity and cerebral ischemia injury

AIM: To study the effects of 9-(4-ethoxycarbonylphenoxy)-6,7-dimethoxy-1,2,3,4-tetrahydro acridine (EDT) on free radical induced injury in primary cultured rat cortical neuron and cerebral ischemia in mice. METHODS: In primary rat cortical neuron, free radical injury model was established by 10 mumol.L-1 H2O2. The content of malondiadehyde (MDA) and activity of superoxide dismutase (SOD) in cells were investigated. Chronic cerebral ischemia model was produced by occlusion of one carotid artery and pneumogastric nerve in mice. The step down test was adopted to investigate the effect of EDT on the memory impairment. The cerebra morphology and MDA, NO content and SOD activity in mice cerebra were detected. RESULTS: In primary rat cortical culture, 0.01-3 mumol.L-1 EDT concentration-dependently inhibited the formation of MDA and reduction of SOD activity induced by 10 mumol.L-1 H2O2. In chronic cerebral ischemia, EDT 2.5, 5 and 10 mg.kg-1 ig for 5 d greatly improved the memory impairment, reduced NO efflux and MDA content, while increased SOD activity in mice cerebra. CONCLUSION: EDT was found to protect neurons from H2O2-induced neurotoxicity and inhibit chronic cerebral ischemia mediated injury and memory impairment in mice.