摘要
目的探讨盐酸非那嗪奈(fenazinel dihydrochloride,FD)对大鼠局灶性脑缺血损伤的保护作用及其机制。方法线拴法制备大鼠中动脉局灶性脑缺血(24h)模型。测定脑梗死面积;检测缺血组织中超氧化物歧化酶(SOD)活性以及丙二醛(MDA)、乳酸(LA)含量;观察组织病理学改变。制备大鼠原代神经元细胞撤血清损伤模型及N-甲基-D-门冬氨酸(NMDA)损伤模型,检测FD对损伤细胞死亡率、SOD活性及MDA、LA含量的影响。结果FD可明显降低脑梗死面积,升高组织中SOD活性,降低MDA、LA含量,减轻脑组织病理学损害;在细胞水平上,FD降低损伤细胞死亡率,升高SOD活性,降低MDA、LA含量。结论FD对大鼠局灶性脑缺血损伤具有明显的保护作用,其机制与降低兴奋性氨基酸损伤、清除氧自由基及改善能量代谢有关。
Aim To investigate the protective effect of fenazinel dihydrochloride （FD） on focal cerebral ischemia injury in rats and to explore its possible mechanism. Methods Middle cerebral artery occlusion （MCAO） was used to induce focal cerebral ischemia model. After 24 h ischemia, the infarct area was determined by the method of TI＇C staining, and the ischemia brains of some other rats were used for measurements of super oxide dismutase （SOD） activity, malondialdehyde （MDA） content, lactic acid （LA） content and the histopathological change. Cortical neurons of fetal rats were cultured in vitro. The protective effects of FD on injuries by treating cells with FBS retraction medium and with N-methyl-D-aspartic acid （NMDA） were observed by determinations of cell death rate, activity of SOD and change of MAD/LA level. Results FD decreased the infract area in MCAO model, increased the activity of SOD in brain, lowed the MDA/LA level, and protected against the brain histological injury. In neuron cells, FD not only increased neuron survival rate and activity of SOD, but also downregulated the MDA/ LA level. Conclusion FD is able to protect cerebral ischemia with involvement of decreasing NMDA level, attenuating oxygen-derived free radicals and improving energy metabolism.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2009年第6期716-720,共5页
Chinese Pharmacological Bulletin
基金
国家高技术研究发展计划(863计划)重大专项基金资助项目(No2006AA02Z4C1)
关键词
盐酸非那嗪奈
局灶性脑缺血
大鼠皮质神经元细胞
fenazinel dihydrochloride
focal cerebral ischemia
rat cerebral cortical neurons
