摘要
目的观察选择性诱生型一氧化氮合酶抑制剂氨基胍(aminoguanidine,AG)对局灶性脑缺血大鼠脑线粒体损伤的作用,探讨其改善缺血性脑损伤的作用机制。方法将大鼠随机分为假手术组、缺血对照组、AG治疗组,采用线栓法复制大鼠大脑中动脉栓塞(MCAO)模型,分别于缺血后2、6、12h给药治疗3d,迅速断头取脑,差速离心法提取缺血侧脑组织线粒体,测定线粒体总ATP酶、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSHPx)活性,以及线粒体一氧化氮(NO)、丙二醛(MDA)含量;电镜观察了缺血后皮层神经元超微结构的改变及AG对此改变的影响。结果在大鼠MCAO后线粒体NO生成明显增加,线粒体总ATP酶、SOD、GSHPx活性均有明显下降,线粒体MDA含量明显升高;缺血2、6、12h给予AG治疗3d与缺血对照组相比NO生成有所下降,总ATP酶、SOD、GSHPx活性均升高,MDA含量下降。电镜结果显示脑缺血后皮层神经元水肿,线粒体肿胀、嵴断裂、溶解、消失,且随缺血时间延长损伤加重;AG能明显改善脑缺血引起的神经元水肿、线粒体肿胀和空泡化。结论AG能明显抑制脑缺血后线粒体NO生成,改善线粒体能量供应,增加线粒体抗氧化作用,从而减轻脑缺血损伤。
Aim To examine the effect of selective inducile nitro oxide synthase inhibitor, aminoguanidine （AG） , on mitochondria injury in focal cerebral ischemia rats. Methods Rats were randomly devided into sham, ischemia and AG treatment groups. The model of focal cerebral ischemia in rats was prepared with thread embolism. AG was administered respectively at 2,6,12 h after MCAO. Rats were killed and mitochondria of cerebral tissue were isolated with differential centrifugation 3 d after AG treatment. Activities of ATPase, SOD and GSH-Px and contents of NO and MDA in mitochondria were measured. Ultrastructure changes of neuronal mitochondria were examined with electronic microscope after the ischemia and AG treatment. Restilts The contents of mitochondria NO and MDA markedly increased. The activities of mitochondria ATPase,SOD and GSH-Px markedly decreased in MCAO rats. Compared with ischemia group, the activities of ATPase, SOD and GSH-Px in mitochondria enhanced and the contents of NO and MDA in mitochondria decreased in ischemia 2,6,12 h group administered with AG. The study showed that the neuronal cytoplasm and the mitochondria swelled, the cristae were disrupted, dissolved or disappeared in MCAO rats. AG ameliorated these injuries induced by cerebral ischemia in rats. Conclusion AG can inhibit the production of NO, beneficially improve mitochondria energy pump and ameliorate oxidative injury after cerebra ischemia, and thus effectively protect brain damage induced by focal cerebral ischemia.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2005年第12期1501-1504,共4页
Chinese Pharmacological Bulletin
基金
河北省自然科学基金资助项目(NoC2005000840)
关键词
脑缺血
线粒体
氨基胍
超微结构
cerebral ischemia
mitochondria
aminoguanidine
ultrastructure
