二氢麦角碱升高血管性痴呆小鼠海马cAMP和腺苷环化酶

目的观测血管性痴呆小鼠海马组织环磷酸腺苷(cAMP)和腺苷环化酶(AC)水平及二氢麦角碱对其的影响,探讨血管性痴呆发病的分子生物学机制。方法通过双侧颈总动脉线结、连续3次缺血-再灌注,制作血管性痴呆动物模型,并设立假手术组、二氢麦角碱组;术后29 d、30 d分别测试学习和记忆成绩;应用放射免疫法检测小鼠海马组织cAMP水平,应用原位杂交技术检测AC水平。结果与假手术组比较,模型组学习和记忆成绩均降低(P<0.05),且海马组织cAMP水平也降低(P<0.05),海马CA1区AC mRNA阳性神经元比例明显降低(P<0.05);而与模型组比较,二氢麦角碱组学习和记忆成绩均改善(P<0.05),且海马组织cAMP水平也升高(P<0.05),海马CA1区AC mRNA阳性神经元比例明显增加(P<0.05)。结论海马组织cAMP和AC水平降低可能参与了血管性痴呆的分子生物学发病机制;二氢麦角碱可以升高其cAMP和AC水平而改善临床症状。

Dihydroergocriptine increase levels of cAMP and adenylyl cyclase in hippocampus of mice with vascular dementia

Objective To observe the levels of cAMP and adenylyl cyclase(AC) in hippocampus of mice with vascular dementia(VD) and the effect of Dihydroergocriptine(DHE),and to explore the molecular pathogenesis of VD.Methods The mice were subjected for ischemia-reperfusion three times on bilateral common carotid arteries by knots to establish models of VD and the changes of learning and memory were tested on d29/d30 after operation.DHE was administrated to another group of mice,which was taken as treatment group.The cAMP level was evaluated by the radioimmunoassay;AC mRNA positive neurons of hippocampus CA1 area were examined through in-situ hybridization.Results Compared with shamed-operation group,the learning and memory of model group was worse(P<0.05),the cAMP level in hippocampus was lower(P<0.05) and the percentage of AC mRNA positive neurons reduced(P<0.05);compared with model group,the learning and memory of DHE group was better(P<0.05),the cAMP level in hippocampus was higher(P<0.05) and the percentage of AC mRNA positive neurons increased(P<0.05).Conclusion The lower levels of cAMP and AC in hippocampus might participate in the molecular pathogenesis of VD;DHE could increase the levels of cAMP and AC and then ameliorate the clinical symptom.