Agrin在脑卒中后运动促进突触再生中的作用及其初步机制研究

发布时间：2019-01-26 08:50

【摘要】：目的:观察脑缺血再灌注损伤后早期运动训练对突触再生的影响,探讨Agrin在脑缺血后运动促进突触再生中的作用以及潜在的调控机制。方法:采用雄性SD大鼠,构建60min的左侧大脑中动脉栓塞再灌注(middlecerebral artery occlusion,MCAO)模型。实验共分为三组:假手术组(Sham)、缺血未运动组(non-exercise group,NE)、缺血早期运动训练组(early exercise group,EE)。Sham 组和NE组大鼠不进行训练,EE组大鼠在MCAO后24h介入运动训练强度逐步增强的跑步训练,每天30min,持续14d。在脑缺血再灌注损伤后相应时间节点,采用神经功能缺失评分法评估大鼠神经功能缺失症状,通过Open field和Elevated plus maze方法评估大鼠手术后的焦虑水平和自发运动能力。此外,通过TTC和CV染色法检测大鼠脑梗死体积;综合运用Western Blot和免疫荧光技术研究运动训练对Agrin表达时间窗及细胞定位的影响,并分析Agrin表达与突触再生的关系。结果:1、与NE组相比,EE组的大鼠神经功能缺失症状得到明显缓解,手术后的焦虑水平明显降低,但是对于自发运动能力的恢复没有显著的促进作用;2、与改善行为学结果一致的是,EE组显著减少缺血大鼠的脑梗死体积、脑水含量;3、Western Blot和Immunofluorescence结果显示,早期运动训练显著促进突触相关蛋白表达,上调神经营养因子水平,促进突触再生;4、Agrin可能是运动训练促进突触再生的重要蛋白。结论:1、脑卒中后早期运动训练能够减少梗死体积,促进神经功能恢复。2、脑卒中后早期运动训练能够促进突触再生相关蛋由的表达。3、脑卒中后早期运动训练上调了促突触再生蛋白Agrin的表达。
[Abstract]:Aim: to investigate the effect of early exercise training on synaptic regeneration after cerebral ischemia-reperfusion injury and to explore the role of Agrin in promoting synaptic regeneration after cerebral ischemia. Methods: male SD rats were used to construct the left middle cerebral artery occlusion reperfusion (middlecerebral artery occlusion,MCAO) model of 60min. The experiment was divided into three groups: sham operation group (Sham),) without exercise group (non-exercise group,NE), early ischemic exercise group (early exercise group,EE). Sham group) and NE group (rats) were not trained. In EE group, the intensity of exercise training increased 24 hours after MCAO, 30 minutes per day for 14 days. At the corresponding time points after cerebral ischemia-reperfusion injury, neurologic deficit scores were used to evaluate the neurological deficit symptoms in rats, and Open field and Elevated plus maze methods were used to assess the level of anxiety and spontaneous motor ability of rats after operation. In addition, the infarct volume of rat brain was detected by TTC and CV staining, and the effects of exercise training on Agrin expression time window and cell location were studied by Western Blot and immunofluorescence technique, and the relationship between Agrin expression and synaptic regeneration was analyzed. Results: 1.Compared with NE group, the neurological deficit symptoms in EE group were obviously alleviated, and the anxiety level was significantly decreased after operation, but there was no significant effect on the recovery of spontaneous motor ability. 2. In accordance with the results of behavior improvement, EE group significantly reduced the cerebral infarction volume and the content of cerebral water in ischemic rats. The results of Western Blot and Immunofluorescence showed that early exercise training could significantly promote the expression of synaptic related proteins, upregulate the level of neurotrophic factors and promote synaptic regeneration, while Agrin might be an important protein in promoting synaptic regeneration during exercise training. Conclusion: 1. Early exercise training after stroke can reduce the volume of infarction and promote the recovery of neural function. 2. Early exercise training after stroke can promote the expression of synaptic regeneration related egg. Early exercise training after stroke upregulated the expression of synaptic regeneration protein Agrin.
【学位授予单位】：昆明理工大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R743.3

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