miR-132调控神经环路-突触可塑性与改善卒中后痴呆的机制研究

Study on the mechanism of miR-132 in the brain and peripheral blood of rats with dementia after stroke and its effect on the model behavior

目的分析卒中后痴呆大鼠模型脑内和外周血中的miR-132的表达以及其对模型行为学的影响,并探讨其可能的机制。方法选取48只大鼠,建立卒中后痴呆的大鼠模型,实验分为4组,其中一组为模型组,另外3组为对照组,然后分别对4组大鼠的行为进行检测,探究miR-132对卒中后痴呆大鼠的影响及其可能的作用机制。结果水迷宫实验提示miR-132对卒中后痴呆大鼠的行为学有改善作用,同时大鼠旷野试验行为检测结果提示agomir-132组的大鼠垂直得分及水平得分均高于模型组(P<0.05),说明miR-132可改善卒中后痴呆相关的额叶-皮质下神经环路的突触可塑性,从而改善PSD小鼠认知功能;agomir-132+Grin2A组的大鼠垂直得分以及水平得分均明显低于其阴性对照(agomir-132+vector)和agomir-132组(P<0.05),并且agomir132+Grin2A组糖水消耗百分比明显低于其阴性对照和agomir-132组(P<0.05),表明Grin2A参与了miR-132对卒中后痴呆大鼠的治疗作用,Grin2A基因的表达可以抑制miR-132调控突触可塑性。结论 miR-132通过改善额叶-皮质环路突触的可塑性,改善卒中后大鼠的认知功能,Grin2A可以阻断miR-132对卒中后痴呆大鼠行为学的改善作用。

ObjectiveTo investigate the expression of miR132in the brain and peripheral blood of rats with dementia after stroke and its effect on the model behavior and to explore possible mechanism.Methods48rats were divided into three groups,one group was the model group,the other was the control group,and then the model rats were established.Then the behavior of the rats in the four groups were detected by the methods of behavior test,To explore the effect of miR132on dementia rats after stroke and the possible mechanism.ResultsWater maze test showed that miR132improved behavior of rats with dementia after stroke.The open field test above behavior of rats showed vertical and horizontal scores in miR132blocking effect on the behavior of dementia rats after stroke was significantly higher than that of the model group.miR132could improve synaptic plasticity on the frontal cortex neural circuits in dementia rats after stroke.Negative control hierer in order to determine whether Grin2A was involved in miR132to improve the effect of learning behavior in dementia rats after stroke,the expression plasmid containing Grin2A gene by intracerebroventricular injection of post stroke dementia rat brain,found that the score of the rats in the agomir132+Grin2A group and the level of vertical score was significantly lower than that of the negative control(agomir132+vector)and agomir132group(P<0.05).And the percentage of sugar consumption in agomir132+Grin2A group was significantly lower than that in the negative control group and agomir132group(P<0.05).The results suggest that Grin2A was involved in the therapeutic effect of miR132on post stroke dementia rats.ConclusionMiR132is an effective tool for the improvement of dementia after stroke.miRl32regulation of neural circuits synaptic plasticity is of great significance in the understanding and treatment of some neurodegenerative diseases.