有氧运动对血管性脑痴呆小鼠学习记忆能力的影响

目的探讨有氧运动对血管性脑痴呆小鼠记忆能力的影响及其作用机制。方法暴露小鼠双侧颈总动脉,重复夹闭动脉3次,尾静脉放血建立血管性脑痴呆小鼠模型,小鼠随机分为三组:假手术组、模型组和有氧运动组。术后第二天开始进行有氧运动,连续7周。训练结束后进行行为学检测,术后30天收集小鼠脑组织样本(海马、前额叶、全脑和血清)。HE染色观察海马CA1区的病理学变化、TUNEL法检测海马CA1区神经细胞凋亡、Western blot和紫外分光光度计检测Bcl-2、Bax、丙二醛(MDA)、超氧化物歧化酶(SOD)、生长相关蛋白(GAP-43)、脑源性神经营养因子(BDNF)、乙酰胆碱合成酶(ACHE)、乙酰胆碱转移酶(CHAT)、突触素(SYP)、神经细胞黏附分子(NCAM)及神经细胞黏附分子受体(NR2B)的变化。结果与假手术组相比,模型组小鼠的僵直时间显著缩短,CA1区神经元细胞病变严重,凋亡细胞增加,MDA和ACHE蛋白的表达明显上升,SYP、NCAM、NR2B、SOD、BDNF、CHAT、GAP-43和Bcl-2蛋白表达降低,Bax蛋白表达没有明显变化。与模型组相比,有氧运动组小鼠的僵直时间显著延长,海马区的组织病变情况改善,且凋亡细胞减少,MDA和ACHE蛋白的表达明显降低,SYP、NCAM、NR2B、SOD、BDNF、CHAT、GAP-43和Bcl-2蛋白的表达升高,Bax蛋白表达没有明显变化。结论有氧训练可能通过上调Bcl-2、SOD、BDNF、CHAT、GAP-43、SYP、NCAM及NR2B蛋白表达,下调MDA和ACHE蛋白表达,减少自由基损伤和海马区神经元细胞凋亡,从而改善血管性痴呆小鼠的学习记忆功能。

Effects of aerobic exercise on learning and memory ability of vascular dementia mice

Aim To study the effect of aerobic exercise on memory ability of mice with vascular dementia. Methods To expose the bilateral common carotid arteries of KM mouse, repeatedly occlusion of common carotid artery and blood letting in caudal vein were made to establish a mouse model of vascular dementia. The mice were randomly divided into three groups:sham group, model group, and aerobic exercise group. Aerobic exercise began on the second day after operation for 7 weeks. Behavioral tests were performed after the training. Brain tissue samples (hippocampus, prefrontal lobe, whole brain and serum) were collected 30 days after the operation. The pathological changes of hippocampal CA1 region were observed by HE staining. The apoptosis of hippocampal CA1 region was detected by TUNEL method. Western blot and ultraviolet spectrophotometer were used to detect the expression of Bcl-2, Bax, malondialdehyde (MDA), superoxide dismutase (SOD), growth-related protein-43 (GAP-43), brain-derived neurotrophic factor (BDNF), acetylcholine synthase (ACHE), acetylcholine transferase (CHAT), synaptophysin (SYP), nerve cell adhesion molecule (NCAM) and nerve cell adhesion molecule receptor 2B (NR2B). Results Compared with the sham group, the time of fear memory in the model group was significantly shortened. The neuronal cells in the hippocampus of the model group were severely damaged and the number of apoptotic cells was increased, the expression of MDA and ACHE protein was significantly increased, the levels of synaptophysin, NCAM, NR2B, SOD, BDNF, CHAT, GAP-43 and Bcl-2 protein expression decreased, Bax protein expression did not change significantly. Compared with the model group, the time of fear memory in the aerobic exercise group was significantly prolonged, the histopathological changes in the hippocampus of the brain were improved, the number of apoptotic cells was decreased, the expression of MDA and ACHE protein was significantly decreased, and the levels of synaptophysin, NCAM, NR2B, SOD, BDNF, CHAT, GAP-43 and Bcl-2 protein expression increased, while Bax protein expression did not change significantly. Conclusion Aerobic training may improve the learning and memory function of vascular dementia mice by up-regulating the expression of Bcl-2, SOD, BDNF, CHAT, GAP-43, SYP, NCAM and NR2B, down-regulating the expression of MDA and ACHE, reducing the damage of free radicals and apoptosis of hippocampal neurons.