氢化麦角碱对血管性痴呆小鼠海马组织Ca M、Ca MPKⅡ mRNA动态表达的影响

Effects of Dihydroergotoxine Mesilate on the Dynamic Expression of CaM,CaMPKⅡ mRNA in Hippocampal Neurons of Mice with Vascular Dementia

目的观察氢化麦角碱对血管性痴呆(VD)小鼠海马组织钙调蛋白(CaM)、钙调蛋白依赖性蛋白激酶Ⅱ(CaMPKⅡ)mRNA表达的影响。方法采用双侧颈总动脉线结法制作小鼠VD模型。将小鼠分为假手术对照组、氢化麦角碱治疗组和VD模型组,分别于术后7、14、30 d测试小鼠学习成绩,24 h后测试记忆成绩,并应用RT-PCR技术检测海马CaM、CaMPKⅡmRNA的动态表达。结果术后7、14、30 d VD模型组海马组织CaM、CaMPKⅡmRNA的表达均低于假手术组(P<0.05);术后7 d氢化麦角碱组CaM、CaMPKⅡmRNA的表达与VD模型组比较差异无统计学意义(P>0.05),但随着用药时间延长,其表达呈逐渐上升的趋势,术后14、30 d氢化麦角碱组CaM、CaMPKⅡmRNA的表达显著高于VD模型组(P<0.05)。结论VD小鼠海马组织CaM、CaMPKⅡmRNA在较长时期内表达减少可能与VD发病相关,而氢化麦角碱可以提高CaM、CaMPKⅡmRNA的表达水平,并改善VD的临床症状。

Objective To investigate the dynamic expression of calmodulin （CAM） and calmodulin-dependent protein kinase Ⅱ （CaMPK Ⅱ ） gene in hippocampal neurons of the mice with vascular dementia （VD） and the effects of dihydroergotoxine mesilate on VD. Methods 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. The treating group was administrated with dihydroergotoxine mesilate after the establishment of VD model. The behavior changes were observed through the step-down avoidance test and water maze test on the 7 th, 14 th and 30 th day after operation, respectively. RT-PCR technique was used to measure the dynamic expression of CaM and CaMPK Ⅱ mRNA in hippocampal neurons. Results The expressions of CaM and CaMPK Ⅱ mRNA in VD groups were significantly reduced than those in control groups on the 7 th（ P 〈0.01）, 14th（P〈0.01） and 30 th（P〈0.05）day after operation. There was no significant difference between the treating group and the VD group on the 7 th day after operation, but with using dihydroergotoxine mesilate, the expressions of CaM and CaMPK Ⅱ mRNA appeared an upregulating trend, the expressions in treating groups were apparently higher than that of VD groups on the 14 th （P〈0.05） and 30 th （P〈0. 01） day after operation. Conclusions Our study suggest that the lower expression of CaM and CaMPK Ⅱ mRNA in hippocampal neurons during a relatively longer time might participate in the pathogenesis of VD. Dihydroergotoxine mesilate may increase the expressions of CaM and CaMPK Ⅱ mRNA and improve the clinical symptoms of VD.