跑台运动对血管痴呆大鼠学习记忆的影响及其作用机制

Effects of treadmill exercise on learning and memory of the vascular dementia rats and its mechanism

目的 观察4周低强度跑台运动对血管痴呆(VD)大鼠空间学习记忆能力,前额叶皮质(PFC)氨基酸水平及蛋白激酶A(PKA)/环磷酸腺苷反应元件结合蛋白(CREB)/脑源性神经营养因子(BDNF)信号通路蛋白表达的影响。方法 39只SD大鼠随机分为假手术组(sham,n=13)、血管痴呆组(VD,n=13)及血管痴呆运动组(VD+EX,n=13)。VD组及VD+EX组大鼠采用双侧颈总动脉永久性结扎法制备慢性脑缺血大鼠模型,然后VD+EX组大鼠进行4周低强度跑台运动。运动结束后,利用水迷宫实验(MWM)评估大鼠学习记忆能力,高效液相色谱法(HPLC)检测大鼠PFC区神经递质谷氨酸(Glu)及γ-氨基丁酸(GABA)水平,利用Western blotting检测大鼠PFC组织PKA、CREB及BDNF蛋白表达。结果 MWM实验结果显示,VD组大鼠第1~5天平均逃避潜伏期较假手术组显著增加,初次找到原平台时间延长,穿越平台次数显著下降(P<0.01)。经过4周低强度跑台运动,VD+EX组大鼠第1~5天平均逃避潜伏期较VD组显著下降,初次找到原平台时间缩短,穿越平台次数显著增加(P<0.01,P<0.05)。HPLC及Western blotting检测显示,与sham组比较,VD组大鼠PFC区Glu、GABA水平及PFC组织PKA、CREB及BDNF蛋白表达均显著下降(P<0.01);与VD组大鼠比较,VD+EX组大鼠PFC区Glu水平及PFC组织PKA、CREB及BDNF蛋白表达均显著增加(P<0.01,P<0.05),GABA水平两组之间差异无显著性(P>0.05)。结论 4周低强度跑台运动可通过增加VD大鼠Glu的释放,并激活PKA/CREB/BDNF通路提升PFC区BDNF表达,从而改善VD大鼠的学习记忆能力。

Objective To observe the effects of 4-week low intensity treadmill exercise on the learning and memory,amino acid levels and the protein expression of protein kinase A(PKA),cyclic adenosine monophosphate response element binding protein(CREB)and brain-derived neurotrophic factor(BDNF)in the prefrontal cortex(PFC)of the vascular dementia(VD)rats.Methods Thirty-nine SD rats were randomly allocated to 3 groups,sham group(sham,n=13),vascular dementia group(VD,n=13)and vascular dementia treaded with exercise group(VD+EX,n=13).Chronic cerebral ischemia model in VD group and VD+EX group rats were established by permanent ligation of bilateral,then VD+EX group rats were submitted to 4-week low intensity treadmill exercise.After exercise,spatial learning and memory ability were evaluated by Morris water maze test(MWM),glutamic(Glu)and gamma-aminobutyric acid(GABA)levels in the PFC were measured by high performance liquid chromatography(HPLC);the protein expression of PKA,CREB and BDNF in the PFC of rats were detected by Western blotting.Results The result of the MWM showed the average escape latency of rats in the VD group on the 1-5 days was significantly higer than sham group,the time to first find the original platform was significantly prolonged and the platform crossings decreased significantly(P<0.01).The average escape latency of rats treated with four-week low intensity treadmill exercise on the 1-5 days was significantly lower than VD group,the time to first find the original platform was significantly shortened and the plaform crossings increased significantly(P<0.O1).HPLC and Western blotting detection showed that the levels of Glu and GABA and the protein expression of PKA,CREB and BDNF in the PFC decreased significantly in VD group rats when compared with sham group(P<0.01).Glu level and the protein expression of PKA,CREB and BDNF in the PFC of rats increased significantly(P<0.05)in VD+EX group rats when compared with VD group rats,but GABA level was not significant difference(P>0.05)between the two groups.Conclusion Four-week low-intensity running exercise improves the learning and memory ability of VD rats through enhancing the Glu level and activating PKA-CREB-BDNF signaling in the PFC of rats.