Li Shao-Yuan, Rong Pei-Jing, Gao Guo-Jian, Zhang Yue, Wang Jun-Ying, Wang Yu, Li Liang, Zhang Jin-Ling, Guo Xiao
Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Bejing 100700, China.
China Academy of Chinese Medical Sciences, Bejing 100700.
Zhen Ci Yan Jiu. 2019 Aug 25;44(8):554-9. doi: 10.13702/j.1000-0607.190292.
To observe the effect of auricular electroacupuncture (EA) on intracellular Raf/ extracellular signal-regulated kinase (ERK)/ ribosomal S6 kinase (RSK)/ cAMP response element-binding protein (CREB) signal pathway in the hippocampus of depression model rats, so as to explore its anti-depressive mechanism.
A total of 60 male SD rats were randomly divided into control, model, auricular EA, PD98059(ERK inhibitor), DMSO (Dimethylsulfoxide), PD98059+EA groups (=10 in each group). The rats in the control group were fed with normal diet without any treatment. The depression model was induced by chronic unpredictable mild stress (CUMS) for consecutive 21 days. EA (20 Hz, 2 mA) was applied to bilateral auricular "Xin"(Heart) and "Shenmen" for 30 min, once daily for 28 days. Rats of the PD98059, DMSO and PD98059+EA groups received intracerebroventricular injection of PD98059(100 µmol/L), DMSO and PD98059 (dissolved by DMSO) solutions (5 µL/d), respectively, once daily for 28 days. Sucrose preference test (sucrose consumption) was conducted at the baseline, before and after the intervention. The expression of hippocampal Raf, phosphorylated (p)-Raf, ERK, p-ERK, RSK, CREB and p-CREB proteins were detected by Western blot after EA intervention.
Following modeling, the sucrose consumption volume, and the expression levels of hippocampal Raf, p-Raf, ERK, p-ERK, RSK, CREB, p-CREB proteins were significantly lower in the model group than those in the control group (<0.01). Following the treatment, the sucrose consumption and the expression levels of Raf, p-Raf, ERK, p-ERK, RSK, CREB, p-CREB in the auricular EA group and those of p-Raf, ERK and CREB in the PD98059+EA group were obviously increased in comparison with the model group (<0.05, <0.01), the expression level of p-ERK in the PD98059 group was obviously decreased in comparison with the model group (<0.05), suggesting an improvement of depression after auricular EA. Compared with auricular EA group, the expression level of p-ERK, p-CREB and RSK in the PD98059+EA group were significantly decreased (<0.05).
EA of auricular "Xin" and "Shenmen" is able to improve depression in depression rats, which is probably related to its effect in promoting activities of hippocampal Raf/ERK/RSK/CREB signaling.
观察耳穴电针(EA)对抑郁模型大鼠海马细胞内Raf/细胞外信号调节激酶(ERK)/核糖体S6激酶(RSK)/环磷酸腺苷反应元件结合蛋白(CREB)信号通路的影响,以探讨其抗抑郁机制。
将60只雄性SD大鼠随机分为对照组、模型组、耳穴电针组、PD98059(ERK抑制剂)组、二甲基亚砜(DMSO)组、PD98059+EA组(每组10只)。对照组大鼠给予正常饮食,未作任何处理。采用慢性不可预测性温和应激(CUMS)连续造模21天。耳穴电针组给予双侧耳穴“心”和“神门”20Hz、2mA电针刺激30分钟,每日1次,共28天。PD98059组、DMSO组和PD98059+EA组大鼠分别侧脑室注射PD98059(100μmol/L)、DMSO及用DMSO溶解的PD98059溶液(5μL/d),每日1次,共28天。在干预前、基线期及干预后进行蔗糖偏好试验(蔗糖消耗量)。耳穴电针干预后,采用蛋白质免疫印迹法检测海马Raf、磷酸化(p)-Raf、ERK、p-ERK、RSK、CREB及p-CREB蛋白的表达。
造模后,模型组大鼠蔗糖消耗量及海马Raf、p-Raf、ERK、p-ERK、RSK、CREB、p-CREB蛋白表达水平均显著低于对照组(<0.01)。治疗后,耳穴电针组蔗糖消耗量及Raf、p-Raf、ERK、p-ERK、RSK、CREB、p-CREB蛋白表达水平,PD98059+EA组p-Raf、ERK、CREB蛋白表达水平较模型组明显升高(<0.05,<0.01);PD98059组p-ERK蛋白表达水平较模型组明显降低(<0.05),提示耳穴电针可改善抑郁状态。与耳穴电针组比较,PD98059+EA组p-ERK、p-CREB、RSK蛋白表达水平显著降低(<0.05)。
耳穴“心”和“神门”电针可改善抑郁大鼠的抑郁状态,其机制可能与促进海马Raf/ERK/RSK/CREB信号通路的活性有关。