Influence of electroacupuncture preconditioning on cognitive function and adenosine monophosphate-activated protein kinase signaling pathway in depression model rats after electroconvulsive therapy
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摘要:目的 探讨电针预处理对抑郁模型大鼠电休克治疗后认知功能及腺苷酸活化蛋白激酶(AMPK)信号通路的影响。方法 将75只雄性SD大鼠随机分为正常对照组(Ⅰ组)、模型组(Ⅱ组)、电休克组(Ⅲ组)、电针+电休克组(Ⅳ组)、Sham+电休克组(Ⅴ组)，每组15只。Ⅱ~Ⅴ组采用慢性不可预见轻度应激(CUMS)方法建立抑郁模型。建模成功后, 4组大鼠均采用腹腔注射异丙酚100 mg/kg麻醉。Ⅱ组仅进行麻醉，不进行电休克治疗，其余3组进行电休克治疗(ECT)。Ⅳ组在ECT治疗前30 min, 先行电针刺百会穴、印堂穴; Ⅴ组在ECT治疗前30 min, 先进行假穴位电针刺激，百会穴、印堂穴旁开5 mm。适应性饲养大鼠7 d后，开始实验(作为实验第1天)。分别于实验的第1、28、40天进行Morris水迷宫实验(定位航行实验和空间探索实验)。实验的第6、33、45天，每组随机选取5只，处死后采用Western blot法测定海马AMKP和磷酸化AMPK(p-AMPK)的表达。结果 与Ⅰ组比较, Ⅱ~Ⅴ组第32天时及Ⅱ组、Ⅲ组、Ⅴ组第44天时的逃避潜伏期和游泳路径明显延长，穿越平台次数明显减少; 与第5天时比较, Ⅱ~Ⅴ组第32天时及Ⅱ组、Ⅲ组、Ⅴ组第44天时逃避潜伏期和游泳路径明显延长，穿越平台次数明显减少; 与Ⅲ组比较, Ⅳ组第44天时逃避潜伏期和游泳路径明显缩短，穿越平台次数明显增多，差异均有统计学意义(P < 0.05)。与Ⅰ组比较, Ⅱ~Ⅴ组第32天时及Ⅱ组、Ⅲ组、Ⅴ组第44天时的海马AMPK、p-AMPK表达水平明显下调; 与第5天时比较, Ⅱ~Ⅴ组第32天时及Ⅱ组、Ⅲ组、Ⅴ组第44天时的海马AMPK、p-AMPK表达明显下调; 与Ⅲ组比较, Ⅳ组第44天时海马AMPK、p-AMPK表达明显上调，差异均有统计学意义(P < 0.05)。结论 电针预处理可改善抑郁模型大鼠ECT后的学习记忆能力，有较好的抗抑郁作用，其机制可能与上调海马AMPK信号通路的表达有关。Abstract:Objective To explore the influence of electroacupuncture preconditioning on cognitive function and adenosine monophosphate-activated protein (AMPK) signaling pathway in depression model rats after electroconvulsive therapy (ECT).Methods Totally 75 male sprague-dawley rats were randomly divided into normal control group (groupⅠ), model group (group Ⅱ), electroconvulsive therapy group (group Ⅲ), electroacupuncture+electroconvulsive therapy group (group Ⅳ), false electroacupuncture+electroconvulsive therapy group (group Ⅴ), with 15 rats in each group. GroupⅡ~Ⅴ were treated by chronic unpredictable mild stress (CUMS) to establish model of depression. After successful modeling, all rats in the four groups were anesthetized with 100 mg/kg by intra-peritoneal injection of propofol. Group Ⅱ was treated by anesthesia without electroconvulsive therapy, the other three groups were treated by electroconvulsive therapy. Group Ⅳ was treated by electric acupuncture at Bai hui (GV20) and Yin tang (GV29) acupoint for 30minutes before ECT. Group Ⅴ was treated by false electric acupuncture at 5 mm next to Bai hui (GV20) and Yin tang (GV29) acupoint for 30 minutes before ECT. The rats were kept adaptively feeding for seven days, then the experiment started (the first day of the experiment). Morris water maze test (positioning navigation experiment and space exploration experiment) was carried out on the 1st day, the 28th day and the 40th day of the experiment respectively. On the 6th day, the 33rd day and the 45th day of the experiment, 5 rats in each group were randomly selected. After the rats were sacrificed, the expressions of AMKP and phosphorylated AMKP (p-AMKP) in the hippocampus were determined by Western blot method.Results Compared with group Ⅰ, the escaping latency and the swimming path extended obviously and the crossing platform number decreased significantly on the 32nd day in group Ⅱ to Ⅴ and the 44th day in group Ⅱ, Ⅲ, Ⅴ. Compared with the result on 5th day, the escaping latency and the swimming path extended obviously and the crossing platform number decreased significantly on the 32nd day in group Ⅱ to Ⅴ and the 44th day in group Ⅱ, Ⅲ, Ⅴ. Compared with group Ⅲ, the escaping latency and the swimming path shortened obviously and the crossing platform significantly increased on the 44th day in group Ⅳ, and there were significant differences (P < 0.05). Compared with group Ⅰ, the expressions of AMPK and p-AMPK in hippocampus significantly reduced on the 32nd day in group Ⅱ to Ⅴ and the 44th day in group Ⅱ, Ⅲ, Ⅴ. Compared with the results on 5th day, the expressions of AMPK and p-AMPK in hippocampus significantly reduced on the 32nd day in group Ⅱ toⅤ and the 44th day in group Ⅱ, Ⅲ, Ⅴ. Compared with group Ⅲ, the expressions of AMPK and p-AMPK in hippocampus increased obviously on 44th day in group Ⅳ, and there were significant differences (P < 0.05).Conclusion Electroacupuncture preconditioning can improve the learningand memory ability of depression model rats after electroconvulsive therapy, and has a good anti-depressant effect. The mechanism may be related to the up-regulation of the expression of AMPK signaling pathway in the hippocampus.
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表 1 各组大鼠逃避潜伏期比较(x±s)
s 组别 实验第5天(n=15) 实验第32天(n=10) 实验第44天(n=5) Ⅰ组 18.00±5.00 19.00±6.00 17.00±8.00 Ⅱ组 17.00±9.00 29.00±7.00*# 27.00±5.00*# Ⅲ组 16.00±6.00 24.00±6.00*# 36.00±9.00*# Ⅳ组 16.00±8.00 26.00±8.00*# 20.00±4.00△ Ⅴ组 17.00±6.00 25.00±4.00*# 32.00±6.00*# Ⅰ组: 正常对照组; Ⅱ组: 模型组; Ⅲ组: 电休克组; Ⅳ组: 电针+电休克组; Ⅴ组: Sham+电休克组。与Ⅰ组比较, *P < 0.05; 与实验第5天比较, #P < 0.05; 与Ⅲ组比较, △P < 0.05。 
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表 2 各组大鼠游泳路径比较(x±s)
cm 组别 实验第5天(n=15) 实验第32天(n=10) 实验第44天(n=5) Ⅰ组 153.00±5.00 158.00±6.00 157.00±8.00 Ⅱ组 156.00±9.00 759.00±27.00*# 722.00±17.00*# Ⅲ组 154.00±6.00 754.00±16.00*# 854.00±33.00*# Ⅳ组 152.00±8.00 696.00±28.00*# 196.00±15.00△ Ⅴ组 151.00±6.00 755.00±34.00*# 785.00±22.00*# Ⅰ组: 正常对照组; Ⅱ组: 模型组; Ⅲ组: 电休克组; Ⅳ组: 电针+电休克组; Ⅴ组: Sham+电休克组。与Ⅰ组比较, *P < 0.05; 与实验第5天比较, #P < 0.05; 与Ⅲ组比较, △P < 0.05。
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表 3 各组大鼠穿越平台次数比较(x±s)
次 组别 实验第5天(n=15) 实验第32天(n=10) 实验第44天(n=5) Ⅰ组 4.21±0.65 4.13±0.26 4.11±2.18 Ⅱ组 4.33±0.89 2.09±0.97*# 2.15±0.44*# Ⅲ组 4.15±0.52 2.11±0.76*# 1.37±0.09*# Ⅳ组 4.38±0.48 2.24±0.08*# 2.93±0.26△ Ⅴ组 4.02±0.16 2.07±0.14*# 1.42±0.13*# Ⅰ组: 正常对照组; Ⅱ组: 模型组; Ⅲ组: 电休克组; Ⅳ组: 电针+电休克组; Ⅴ组: Sham+电休克组。与Ⅰ组比较, *P < 0.05; 与实验第5天比较, #P < 0.05; 与Ⅲ组比较, △P < 0.05。
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表 4 各组大鼠海马AMPK、p-AMPK表达水平比较(x±s)(n=5)
组别 AMPK p-AMPK 实验第5天 实验第32天 实验第44天 实验第5天 实验第32天 实验第44天 Ⅰ组 2.22±0.31 2.48±0.24 2.32±0.31 2.06±0.15 2.12±0.18 2.06±0.21 Ⅱ组 2.35±0.22 0.55±0.11*# 0.52±0.07*# 2.22±0.21 0.35±0.08*# 0.39±0.06*# Ⅲ组 2.07±0.18 0.58±0.06*# 0.25±0.04*# 2.11±0.17 0.37±0.06*# 0.16±0.05*# Ⅳ组 2.13±0.06 0.53±0.14*# 2.13±0.15△ 2.14±0.13 0.33±0.14*# 1.93±0.24△ Ⅴ组 1.98±0.14 0.51±0.13*# 0.28±0.07*# 2.09±0.05 0.38±0.05*# 0.19±0.04*# Ⅰ组: 正常对照组; Ⅱ组: 模型组; Ⅲ组: 电休克组; Ⅳ组: 电针+电休克组; Ⅴ组: Sham+电休克组。AMPK: 腺苷酸活化蛋白激酶; p-AMPK: 磷酸化腺苷酸活化蛋白激酶。与Ⅰ组比较, *P < 0.05; 与实验第5天比较, #P < 0.05; 与Ⅲ组比较, △P < 0.05。
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