[Effect of transcutaneous electrical acupoint stimulation on learning and memory ability of chronic fatigue syndrome rats and its mechanisms].

To observe the effect of transcutaneous electrical acupoint stimulation (TEAS) on the histomorphological manifestations of hippocampal CA1 region and the expression of extracellular regulatory protein kinase (ERK), cyclic adenosine response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in chronic fatigue syndrome (CFS) rats, so as to explore the mechanisms of TEAS in improving the learning and memory abilities of CFS rats.Forty male Wistar rats were randomly divided into normal group (10 rats) and modeling group (30 rats); then after modeling, they were selected and randomly divided into model group (10 rats) and TEAS group (10 rats). CFS rats model was prepared by sleep deprivation combined with weight-bearing swimming. Rats in the TEAS group were stimulated with Han's acupoint nerve stimulator at bilateral "Zusanli" (ST36) and "Shenshu" (BL23) (2 Hz/15 Hz, 1-2 mA), 20 min each time, once a day for 4 weeks with 1 d rest every 6 d. The score of general conditions of rats was evaluated. The learning and memory ability was tested with Morris water maze. The morphology and ultrastructure of hippocampal CA1 region were observed by HE staining and transmission electron microscopy. The expression levels of ERK, CREB and BDNF mRNAs and proteins in hippocampus were detected by real time quantitative PCR and Western blot, respectively.Compared with the normal group, the score of general condition was increased (P<0.01); the escape latency was prolonged (P<0.05, P<0.01) and the times of crossing the original platform was decreased (P<0.05); the expression levels of ERK, CREB and BDNF mRNAs and proteins in hippocampus were decreased (P<0.05, P<0.01) in the model group. Compared with the model group, the scores of general condition on the 42nd and 49th day were decreased (P<0.05, P<0.01); the escape latency was shortened (P<0.01, P<0.05)and the times of crossing the original platform were increased (P<0.05); the expression levels of ERK, CREB and BDNF mRNAs and proteins in hippocampus were increased (P<0.01, P<0.05) in the TEAS group. The morphology of neurons in hippocampal CA1 region was normal in the normal group. In the model group, the number of neurons in hippocampal CA1 region decreased, the arrangement of nerve cells was scattered, the number of apoptotic cells increased, some nuclear structures disappeared, nuclear heterochromatin increased, the cell membrane wrinkled, the chromatin appeared empty bright area, and the crista was incomplete. Compared with the model group, the nerve cells morphology in hippocampal CA1 region was more regular, the number of apoptotic cells decreased, the chromatin and the cytoplasm were uniformly distributed, and the crista was relatively intact in the TEAS group.TEAS can improve the learning and memory ability of CFS rats, the mechanisms may be related to improving the neural structure of hippocampal CA1 region and up-regulating the expression levels of ERK/CREB/BDNF.目的：观察经皮穴位电刺激(TEAS)对慢性疲劳综合征(CFS)大鼠海马CA1区组织形态学表现及细胞外调节蛋白激酶(ERK)、环磷腺苷效应元件结合蛋白(CREB)、脑源性神经营养因子(BDNF)mRNA与蛋白表达的影响，探讨TEAS改善CFS大鼠学习记忆能力的相关机制。方法：Wistar大鼠随机分为正常组、模型组和TEAS组，每组10只。采用睡眠剥夺结合负重游泳法制备CFS大鼠模型。TEAS组在双侧“足三里”“肾俞”连接韩氏穴位神经刺激仪，疏密波，每次20 min，每日1次，连续治疗6 d，休息1 d，共4周。采用实验大鼠一般情况半定量评分观察表评价大鼠一般状况，Morris水迷宫实验观察大鼠学习记忆能力，HE染色与透射电镜观察海马CA1区的组织形态与超微结构，实时荧光定量PCR法与Western blot法检测海马组织中ERK、CREB、BDNF mRNA与蛋白的相对表达量。结果：治疗后与正常组比较，模型组一般情况半定量评分升高(P<0.01)，逃避潜伏期延长(P<0.05，P<0.01)，穿越原平台次数减少(P<0.05)，海马组织中ERK、CREB、BDNF mRNA和蛋白的相对表达量均降低(P<0.05, P<0.01)；与同时点模型组比较，TEAS组第42、49天一般情况半定量评分降低(P<0.05，P<0.01)，逃避潜伏期缩短(P<0.01，P<0.05)，穿越原平台次数增加(P<0.05)，海马组织中ERK、CREB、BDNF mRNA和蛋白的相对表达量均升高(P<0.01，P<0.05)。正常组海马CA1区神经元细胞形态正常；模型组海马CA1区神经元数量减少，神经细胞排列分散，凋亡细胞数量增多，部分细胞核结构消失，核异染色质增多，胞膜出现皱褶，染色质出现空亮区，嵴不完整；与模型组比较，TEAS组海马CA1区神经细胞排列仍有分散，但总体细胞形态较规则，凋亡细胞数量减少，染色质分布均匀，胞质均匀，嵴较完整。结论：TEAS可改善CFS大鼠的学习记忆能力，其作用机制可能与改善海马CA1区的组织结构、上调ERK/CREB/BDNF表达有关。.