双氢麦角碱对血管性痴呆小鼠海马及脑皮质NOS阳性神经元的影响

Effects of dihydroergotoxine on the change of NOS positive neurons in hippocampus and cerebral cortex of mice with vascular dementia

目的:观察双氢麦角碱对血管性痴呆(VD)小鼠海马及脑皮质一氧化氮合酶(NOS)阳性神经元的影响。方法:采用双侧颈总动脉线结再灌注法制作小鼠VD动物模型。将小鼠分为假手术对照组、双氢麦角碱治疗组和VD模型组,分别于术后7d、14d、30d测试小鼠学习成绩,24h后测试记忆成绩,并应用NADPH-d酶组织化学染色法,观察海马及脑皮质NOS阳性神经元的变化特征。结果:术后第7dVD模型组海马及脑皮质NOS阳性神经元的数量较假手术组有所减少,双氢麦角碱组较VD模型组有所增多,但差异无显著性意义(P>0.05);术后第14d、30d模型组海马及脑皮质NOS阳性神经元数量明显低于假手术组(P<0.01),双氢麦角碱组海马及脑皮质NOS阳性神经元的数量显著高于VD模型组(P<0.01)。结论:VD小鼠海马及脑皮质NOS阳性神经元的数量在较长时期内持续减少可能与VD发病相关,而双氢麦角碱可以提高海马及脑皮质NOS阳性神经元的数量,并改善VD的临床症状。

Objective： To investigate the change of nitric oxide synthase （NOS） positive neurons in hippocampus and cerebral cortex of mice with vascular dementia （VD） and the effects of dihydroergotoxine on VD. Method： The mice were subjected for ischemia-reperfusion repeatedly by blocking the bilateral common carotid arteries to establish the VD models. Animals with the shamed-operation were taken as control group. The treating group was administrated with dihydroergotoxine after the establishment of VD model. The behavior changes were observed through the step-down avoidance test and water maze test on the 7th, 14th and 30th days after operation, respectively. A NADPH-diaphorase histochemistry method was used to measure the NOS positive neurons in hippocampus and cerebral cortex of mice. Result： The NOS positive neurons in hippocampus and cerebral cortex of VD group decreased more than those of control group on the 7th day after operation, and those of treating group increased more than VD group, while no significant difference was found （P〉0.05）. With the prolongation of observing time, the NOS positive neurons of VD groups reduced significantly than those of control groups on the 14th and 30th day after operation （P〈0.01）, but with using dihydroergotoxine, the NOS positive neurons of treating groups was apparently higher than those of VD groups （P〈0.01）. Conclusion： Fewer NOS positive neurons in hippocampus and cerebral cortex during a relatively long time might participate in the pathogenesis of VD. Dihydroergotoxine might increase the NOS positive neurons in hippocampus and cerebral cortex and improve the clinical symptoms of VD.