坐骨神经电刺激对慢性脑缺血大鼠海马区血管内皮生长因子表达及学习记忆功能的影响

Effects of electrical stimulation of the sciatic nerve on the expression of vascular endothelial growth factor in the hippocampus and on learning and memory in cases of chronic cerebral hypoperfusion

目的探讨坐骨神经电刺激对慢性脑缺血大鼠学习记忆功能的影响及其可能的作用机制。方法将32只SD大鼠随机分为正常组、假手术组、模型组和刺激组,每组8只。模型组和刺激组采用改良2-VO法建造慢性脑缺血模型。造模成功后,应用Morris水迷宫检测各组大鼠的学习记忆功能,结束后对刺激组大鼠行坐骨神经电刺激干预。干预4周后,再次行Morris水迷宫实验,并采用HE染色观察各组大鼠海马区细胞的形态学变化,免疫组化检测其神经元特异性烯醇化酶(NSE)及血管内皮生长因子(VEGF)的表达。结果干预前,模型组和刺激组大鼠的逃避潜伏期较正常组和假手术组延长,穿越平台次数(穿台次数)减少,目标象限时间缩短,且差异均有统计学意义(P<0.05);干预4周后,刺激组大鼠与组内干预前及同时间点模型组相比,其逃避潜伏期缩短、穿越平台次数增多、目标象限时间延长,且差异有统计学意义(P<0.05)。HE染色发现,模型组大鼠的海马区神经元损伤程度较正常组和假手术组明显加重,刺激组正常神经元数量较模型组增加,损伤程度减轻。免疫组化显示,模型组大鼠海马区NSE及VEGF表达较正常组和假手术组明显降低(P<0.05),刺激组的NSE和VEGF表达均较模型组增高,差异均有统计学意义(P<0.05)。结论坐骨神经电刺激可以改善慢性脑缺血大鼠的学习记忆功能,其作用机制可能与大鼠海马区VEGF的表达增加有关。

Objective To explore how electrical stimulation of the sciatic nerve affects learning and memory in cases of chronic cerebral hypoperfusion and its mechanism.Methods Thirty-two Sprague-Dawley rats were randomly divided into a normal group,a sham-operation group,a model group and a stimulation group,each of 8.In the model and stimulation groups a chronic cerebral hypoperfusion model was established using the modified 2-VO method.The stimulation group then received electrical stimulation of the sciatic nerve for 4 weeks.Afterward all of the rats′learning and memory were tested using the Morris water maze.HE staining and immunohistochemistry were used to observe any morphological change in the hippocampus and the expression of neuron-specific enolase(NSE)and vascular endothelial growth factor(VEGF).Results The model and stimulation groups demonstrated significantly longer escape latency,fewer platform crossing times and shorter target quadrant times than the normal and sham-ope-ration groups before the intervention.All of these indicators had improved after the intervention.According to the HE staining,neuronal damage in the hippocampus was aggravated significantly in the model group compared with the normal and sham-operation groups,while the degree of damage was reduced in the stimulation group.Moreover,the immunohistochemistry results suggested that the expressions of NSE and VEGF were reduced significantly in the model group compared with the normal and sham-operation groups,while in the stimulation group they had increased significantly compared with the model group.Conclusions Electrical stimulation of the sciatic nerve can improve learning and memory in cases of chronic cerebral hypoperfusion,at least in rats.It is probably related to the increased expression of VEGF in the hippocampus.