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针刺干预对慢性不可预测轻度应激诱导抑郁大鼠抑郁行为及前额叶皮质ERK 1/2和BDNF表达的影响

[Effect of Acupuncture Intervention on Depression Behavior and Expression of ERK 1/2 and BDNF in Prefrontal Cortex in Chronic Unpredictable Mild Stress Induced Depression Rats].

作者信息

Li Xiang, Xu Ming-Min, Jiang Hui-Li, Lu Jun, Zhang Xu-Hui, Zhao Bing-Cong, Yang Xin-Jing, Sun Yang, Gao Xing-Zhou, Liang Xing-Chen, Yu Qiu-Yun, Feng Shi-Xing, Li Yu-Fei, Yu Miao, Tu Ya

机构信息

School of Acupuncture-moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing 100029, China; Research Center of Mental and Neurological Disorders, School of Acupuncture-moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing 100029.

Chengdu University of Chinese Medicine, Chengdu 610075.

出版信息

Zhen Ci Yan Jiu. 2018 Nov 25;43(11):705-10. doi: 10.13702/j.1000-0607.180288.

Abstract

OBJECTIVE

To investigate the effect of acupuncture intervention on the depression behavior and expression of extracellular signal-regulated protein kinases (ERK 1/2), p-ERK 1/2 and brain-derived neurotrophic factor (BDNF) in the prefrontal cortex of chronic unpredictable mild stress (CUMS) induced depression rats, so as to explore its antidepressant mechanism.

METHODS

Sixty-four male SD rats were randomly divided into control, model, acupuncture, Fluoxetine, model + Dimethyl sulfoxide (DMSO), model + PD 98059(an ERK pathway inhibitor), acupuncture + PD 98059 and Fluoxetine + PD 98059 groups (=8 rats in each). The CUMS depression model was established by using chronic mild and unpredictable stress methods for 21 days. Manual acupuncture stimulation was applied to "Baihui" (GV 20) and "Yintang" (GV 29) for 10 min before modeling, once daily for 21 days. Fluoxetine hydrochloride suspension (1.8 mg•kg•d) was given to rats of the Fluoxetine group and Fluo-xetine + PD 98059 group by gavage 30 min before CUMS. PD 98059 (dissolved in DMSO, 10 µL) was administered to rats of model + PD 98059 group, acupuncture + PD 98059 and Fluoxetine + PD 98059 group, and DMSO (10 µL) to rats of model + DMSO group by intracerebroventricular injection 1 h before CUMS. Sucrose consumption test was carried out to evaluate the depressive behavior. Western blot was performed to detect the expression of ERK 1/2, p-ERK 1/2 and BDNF of prefrontal cortex.

RESULTS

Compared with the control group, the sucrose consumption and the expression levels of p-ERK 1/2 and BDNF protein in the prefrontal cortex were significantly reduced in the model and model+DMSO group (<0. 01). After the intervention, modeling induced decrease of the sucrose consumption, and p-ERK 1/2 and BDNF expression was significantly up-regulated in both acupuncture and Fluoxetine groups (<0.01, <0.05), but not in the model+PD 98059, Fluoxetine +PD 98059 and acupuncture+PD 98059 groups (>0.05). No significant differences were found among the model+PD 98059, Fluoxetine +PD 98059 and acupuncture+PD 98059 groups in the sucrose consumption, and ERK 1/2, p-ERK 1/2 and BDNF expression levels (>0.05), and in the expression levels of ERK 1/2 protein among the 8 groups (>0.05).

CONCLUSION

Acupuncture intervention has an anti-depressive role in CUMS induced depression rats, which may be related to its effects in up-regulating the expression of p-ERK 1/2 and BDNF in the prefrontal cortex tissue.

摘要

目的

探讨针刺干预对慢性不可预测性温和应激(CUMS)诱导的抑郁大鼠前额叶皮质抑郁行为及细胞外信号调节蛋白激酶(ERK 1/2)、磷酸化细胞外信号调节蛋白激酶(p-ERK 1/2)和脑源性神经营养因子(BDNF)表达的影响,以探讨其抗抑郁机制。

方法

将64只雄性SD大鼠随机分为对照组、模型组、针刺组、氟西汀组、模型+二甲基亚砜(DMSO)组、模型+PD 98059(ERK通路抑制剂)组、针刺+PD 98059组和氟西汀+PD 98059组(每组8只)。采用慢性温和不可预测应激方法建立CUMS抑郁模型,持续21天。造模前对“百会”(GV 20)和“印堂”(GV 29)进行手动针刺刺激10分钟,每天1次,共21天。在CUMS前30分钟,给氟西汀组和氟西汀+PD 98059组大鼠灌胃盐酸氟西汀混悬液(1.8 mg•kg•d)。在CUMS前1小时,给模型+PD 98059组、针刺+PD 98059组和氟西汀+PD 98059组大鼠脑室内注射PD 98059(溶于DMSO,10 μL),给模型+DMSO组大鼠脑室内注射DMSO(10 μL)。进行蔗糖消耗试验以评估抑郁行为。采用蛋白质免疫印迹法检测前额叶皮质ERK 1/2、p-ERK 1/2和BDNF的表达。

结果

与对照组相比,模型组和模型+DMSO组的蔗糖消耗量以及前额叶皮质p-ERK 1/2和BDNF蛋白表达水平显著降低(<0.01)。干预后,造模诱导的蔗糖消耗量降低,针刺组和氟西汀组的p-ERK 1/2和BDNF表达均显著上调(<0.01,<0.05),但模型+PD 98059组、氟西汀+PD 98059组和针刺+PD 98059组未上调(>0.05)。模型+PD 98059组、氟西汀+PD 98059组和针刺+PD 98059组在蔗糖消耗量、ERK 1/2、p-ERK 1/2和BDNF表达水平方面无显著差异(>0.05),8组之间ERK 1/2蛋白表达水平也无显著差异(>0.05)。

结论

针刺干预对CUMS诱导的抑郁大鼠具有抗抑郁作用,这可能与其上调前额叶皮质组织中p-ERK 1/2和BDNF表达的作用有关。

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