重复经颅磁刺激对血管性痴呆大鼠学习记忆功能及海马锥体细胞树突形态的影响

Effects of repetitive transcranial magnetic stimulation on learning, memory and dendrite morphology in the hippocampus

目的观察重复经颅磁刺激（rTMS）对血管性痴呆大鼠学习记忆功能及海马CAl区锥体细胞树突形态的影响，并探讨其可能的作用机制。方法将造模成功后符合标准的36只雄性SD大鼠随机分为对照组、模型组和rTMS组，每组12只。采用两血管阻断法制作血管性痴呆模型。rTMS组于制模成功后给予rTMS治疗。对照组及模型组不给予任何治疗。于造模后第30天采用Morris水迷宫实验检测3组大鼠的学习记忆能力。学习记忆能力测试结束后取大鼠海马组织行Golgi—Cox染色，光镜下观察海马CAl区锥体细胞树突的分支、长度及树突棘密度的变化；应用免疫组织化学方法检测海马CAl区脑源性神经营养因子（BDNF）的表达。结果rTMS组在测试的第1、2、3、4天水迷宫逃避潜伏期分别为（47．32±15．44）S、（37．20±14．76）s、（25．16±11．55）S和（21．48-I-9．90）S，与模型组同时间点相比明显缩短（P〈0．05），rTMS组在原平台象限跨越相应平台次数达（8．25±1．75）次，较模型组明显增多（P〈0．05）；和对照组相比，模型组及rTMS组海马锥体细胞一级树突的分支数、树突总长度及树突棘密度均明显减少，差异均有统计学意义（P〈0．05）。rTMS组海马锥体细胞树突的分支数、树突总长度及单位长度树突棘密度分别为（6．9±1．8）个、（935±108）μm和（0．72±0．19）个／μm，和模型组相比均有显著增加（P〈0．05）。rTMS组BDNF阳性表达细胞数为（23．17±1．17）个／200倍视野，较模型组明显增多，差异有统计学意义（P〈0．05）。结论rTMS能改善血管性痴呆大鼠学习记忆功能，机制可能与rTMS治疗能促进海马CA1区BDNF的表达，从而改善海马CA1区锥体细胞树突形态有关。

Objective To survey the effects of repetitive transcranial magnetic stimulation （rTMS） on learning, memory and the dendrite morphology of neurons in the CA1 area of the hippocampus in rats with vascular dementia. Methods Thirty-six male SD rats were divided into a control group, a model group and a rTMS group randomly, 12 rats in each group. A model of vascular dementia （VaD） was established using the two vessel occlusion method. The rats in the rTMS group were given rTMS treatment. The rats in the other two groups had no therapy. The Morris water maze （MWM） test was used to evaluate the rats＇ learning and memory abilities on the 30th day after the operation. After the MWM test the dendrite morphology of the pyramidal cells in the CA1 area of the hippocampus was detected after Golgi-Cox staining using light microscopy and the expression of brain-derived neurotrophic factor （BDNF） was detected using immunohistochemistry methods. Results The average MWM escape latency in the rTMS group was shorter than in the model group on the 1st, 2rid, 3rd and 4th day. The number of crossings of the platform quadrant in the rTMS group was significantly more than in the model group. The number of branch segments, their total length and the dendritic spine density of pyramidal cell dendrites in the CA1 area of the hippocampus were all significantly lower in the model group than in the control group, but in the rTMS group all these indicators were significantly improvedcompared with the model group. The expression of BDNF in the CA1 area in rTMS group was significantly higher than in the model group. Conclusions rTMS can improve learning and memory in VaD, at least in rats. The mechanism may be associated with rTMS promoting the expression of BDNF in the hippocampus and so improving the dendrite morphology of pyramidal cells.