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目的:观察100 Hz、2 Hz、2 Hz/100 Hz三种频率电针(EA)对血管性痴呆(VD)大鼠海马神经元凋亡和c-jun氨基末端激酶(JNK)信号通路的影响,探讨电针干预VD的效应机制.方法:将50只雄性Sprague-Dawley大鼠随机分为假手术组、模型组、100 Hz电针组、2 Hz电针组和2 Hz/100 Hz电针组,每组10只.采用双侧颈总动脉反复缺血再灌注制备VD模型,造模后各电针组取百会、大椎、膈俞和足三里进行相应频率的电针干预,每天1次,连续14 d.干预结束后,使用Morris水迷宫检测各组大鼠学习记忆成绩;苏木素-伊红染色法观察海马CA1区组织形态学变化;原位末端转移酶标记法(TUNEL)检测海马CA1区神经元凋亡;免疫印迹法检测海马组织JNK、磷酸化JNK(p-JNK)、半胱氨酸蛋白酶-8(Caspase-8)和半胱氨酸蛋白酶-3(Caspase-3)蛋白表达.结果:与假手术组相比,模型组大鼠水迷宫测试逃避潜伏期延长,穿越原平台次数减少(P<0.01);海马区神经元损伤严重,神经元存活数量减少(P<0.01),凋亡神经元增多(P<0.01);海马JNK、p-JNK、Caspase-8和Caspase-3蛋白表达显著升高(P<0.01).与模型组相比,各电针组大鼠逃避潜伏期显著缩短,穿越原平台次数显著增多(P<0.01);海马神经元损伤减轻,神经元存活数量增多(P<0.01),凋亡神经元减少(P<0.01);海马JNK、p-JNK、Caspase-8和Caspase-3蛋白表达降低(P<0.01).2 Hz电针组和2 Hz/100 Hz电针组优于100 Hz电针组(P<0.01).结论:100 Hz、2 Hz和2 Hz/100 Hz三种频率电针均能改善缺血再灌注VD大鼠的学习记忆能力;其机制可能与电针抑制神经元细胞凋亡及调控JNK信号通路相关蛋白表达相关,且2 Hz与2 Hz/100 Hz电针干预效果更显著.“,”Objective: To observe the effects of electroacupuncture (EA) with three frequencies (100 Hz, 2 Hz, and 2 Hz/100 Hz) on the apoptosis of neurons and c-Jun N-terminal kinase (JNK) signaling pathway in the hippocampus of rats with vascular dementia (VD), and explore the mechanism of EA intervention for VD. Methods: Fifty male Sprague-Dawley rats were randomly divided into a model group, a sham operation group, a 100 Hz EA group, a 2 Hz EA group, and a 2 Hz/100 Hz EA group, with ten rats in each group. The VD model rats were established by repeated ischemia-reperfusion of bilateral common carotid arteries. The rats in the EA groups received EA intervention at Baihui (GV20), Dazhui (GV14), Geshu (BL17) and Zusanli (ST36), once a day for 14 d. Afterward, Morris water maze was used to examine the learning and memory performances of the rats in each group, hematoxylin-eosin staining to observe the histomorphological changes in the hippocampal CA1 region, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling to test the apoptosis of neurons in the hippocampal CA1 region, and Western blot to detect the protein expression levels of JNK, phosphorylated JNK (p-JNK), Caspase-8, and Caspase-3 in the hippocampus tissue. Results: Compared with the sham operation group, the escape latency of the model group in water maze test was prolonged; the number of crossing the original platform was decreased (P<0.01); the hippocampal neurons were severely damaged and the number of surviving neurons was decreased (P<0.01), whereas the number of apoptotic neurons was increased (P<0.01); the protein expression levels of JNK, p-JNK, Caspase-8, and Caspase-3 in the hippocampus were significantly increased (P<0.01). Compared with the model group, the escape latency of each EA group was significantly shortened; the number of crossing the original platform was significantly increased (P<0.01); the damage of hippocampal neurons was alleviated, the number of surviving neurons was increased (P<0.01), and the number of apoptotic neurons was decreased (P<0.01); the protein expression levels of JNK, p-JNK, Caspase-8, and Caspase-3 in the hippocampus were decreased (P<0.01). The results in the 2 Hz EA group and the 2 Hz/100 Hz EA group were superior to those in the 100 Hz EA group. Conclusion: EA with the three frequencies (100 Hz, 2 Hz, and 2 Hz/100 Hz) can improve the learning and memory performances in VD rats subjected to ischemia-reperfusion, its mechanism may be related to the inhibition of neuronal apoptosis and the regulation of the related protein expression of JNK signaling pathway, and the intervention effects of EA with 2 Hz and 2 Hz/100 Hz are more significant.