智三针电针改善血管性痴呆大鼠认知功能及机制

Effect of electroacupuncture Zhisan acupuncture on cognitive function of vascular dementia rat and its mechanism

目的观察智三针电针治疗前后血管性痴呆(VD)大鼠空间学习记忆、海马区神经细胞形态、突触膜表面的EphB2/ephrinB3表达的影响,探讨电针智三针改善VD大鼠认知功能机制。方法采用改良四血管阻断法模拟VD大鼠模型,随机分为VD模型组、电针组、尼莫地平组,并设置假手术组作为对照。电针组与尼莫地平组分别予智三针电针和尼莫地平(3 mg/ml)灌胃治疗3 w,休息1 w后Morris水迷宫检测各组大鼠空间学习和记忆能力,取大鼠海马脑组织,镜下观察HE染色下的大鼠海马锥体细胞形态;酶联免疫吸附试验测定血浆干扰素(IFN)-γ,C1q等炎症因子含量,Western印迹测定海马区神经细胞突触膜表面的EphB2/ephrinB3的表达。结果与假手术组比较,VD模型组大鼠水迷宫学习记忆成绩显著降低(P<0.05),海马CA1区坏死凋亡的神经细胞明显增加(P<0.05),血清IFN-γ,C1q等炎症因子含量增加(P<0.05),海马CA1区突触表面EphB2/ephrinB3表达降低(P<0.05)。经智三针电针疗法后,与模型组比较,VD大鼠水迷宫学习记忆成绩显著提高(P<0.05),海马CA1区坏死凋亡的锥体细胞明显减少(P<0.05),血清IFN-γ,C1q含量降低(P<0.05),海马CA1区突触表面EphB2/ephrinB3表达增加(P<0.05)。与尼莫地平组比较,差异无统计学意义(P>0.05)。结论智三针可通过VD大鼠的空间学习记忆能力,其机制可能与其降低脑缺血后血浆炎症因子含量、抑制了海马CA1区神经元的凋亡和通过Eph/ephrin信号通路调控了突触可塑性有关。

Objective To observe the effects of electroacupuncture Zhisan acupuncture on spatial learning and memory, neuronal morphology of hippocampal CA1 area and the expression of EphB2/EphrinB3 protein in synaptic membrane of vascular dementia(VD) rats, and explore the mechanism of improving cognitive function of VD rats.Methods VD rats were made by the modified Pulsinelli′s four vessel blocking method. They were randomly divided into VD model group, electroacupuncture Zhisan acupuncture group and nimodipine group. The sham operation group was set as the control group. The rats in the two treatment groups were given electroacupuncture and nimodipine for 20 days, rest for 7 days. Morris water maze was used to detect the changes of spatial learning and memory ability. After "euthanasia", the hippocampal tissues of rats were taken, the morphological changes of hippocampal neurons were observed by HE staining, the expression of EphB2/EphrinB3 protein in synaptic membrane of hippocampal neurons was detected by Western blot, and the contents of IFN-γ and C1 q in serum were measured by ELISA. Results Compared with the sham operation group, the learning and memory performance of water maze in VD model group decreased significantly(P<0.05). Compared with VD model group, the water maze learning and memory performance of rats in the electroacupuncture Zhisan acupuncture group was significantly improved(P<0.05), the necrotic neurons in hippocampal CA1 area were significantly reduced(P<0.05), the expression of EphB2/EphrinB3 in synaptic membrane was increased(P<0.05), and the content of IFN-γ and C1 q in serum were decreased(P<0.05). There was no significant difference between the electroacupuncture Zhisan acupuncture group and nimodipine group(P>0.05). Conclusions Electroacupuncture of Zhisan acupuncture might increase the expression of Eph/ephrin in synaptic membrane of hippocampal CA1 neurons, decrease the content of IFN-γ and C1 q in serum, reduce the necrosis of hippocampal CA1 neurons, and improve the learning and memory of VD rats.