组织型纤溶酶原激活剂/脑源性神经营养因子通路可能参与电针对慢性不可预测轻度应激诱导的大鼠抑郁症的抗抑郁作用
Possible Involvement of Tissue Plasminogen Activator/Brain-Derived Neurotrophic Factor Pathway in Anti-Depressant Effects of Electroacupuncture in Chronic Unpredictable Mild Stress-Induced Depression in Rats.
作者信息
Luo Tong, Tian Huiling, Song Hongtao, Zhao Jun, Liya Ai, Fang Yumin, Mou Junhui, Li Zhigang, Chaoketu Saiyin
机构信息
Department of Acupuncture, Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, China.
Department of Traditional Chinese Medicine, Inner Mongolia People's Hospital, Hohhot, China.
出版信息
Front Psychiatry. 2020 Feb 20;11:63. doi: 10.3389/fpsyt.2020.00063. eCollection 2020.
OBJECTIVE
Using a rat model of chronic unpredictable mild stress (CUMS), to investigate the effects of electroacupuncture (EA) on the tissue plasminogen activator (tPA)/brain-derived neurotrophic factor (BDNF) pathway.
METHODS
Sixty male Sprague-Dawley rats were randomly divided into four groups: normal, model, fluoxetine (fluox), or EA. Experimental groups were subjected to 28 d of CUMS modeling. One hour after CUMS, the fluox and EA groups were treated with fluox and a 20 min EA intervention, respectively. Depressive-like behaviors were assessed by open field and sucrose preference tests. After the rats were sacrificed, brains were dissected and processed using hematoxylin and eosin (HE) staining to observe changes in the morphology and quantity of neurons in the hippocampal 3 area. Western blot and real-time polymerase chain reaction (PCR) demonstrated the effects of EA on the tPA/BDNF pathway-related molecules in the hippocampi and raphe nuclei.
RESULTS
Compared to the model group, the number of horizontal and vertical movements and the percentage of sucrose consumption in the EA groups were significantly increased (P < 0.01). Compared to the model group, HE staining showed that the hippocampal neurons in the EA and fluox groups were arranged neatly, with rich layers and complete cell structures. The Western blot and real-time PCR showed that the levels of tPA, BDNF, tropomyosin receptor kinase B, and BDNF micro RNA (mRNA) in the hippocampi of the EA group were higher than in the model group (P < 0.01, P < 0.01, P < 0.05, P < 0.01, respectively). The content of p75NTR, proBDNF, and tPA mRNA in the hippocampi of the EA group displayed no significant differences compared to the model group. The tPA mRNA content in the raphe nuclei of the EA group was higher than in the model group (P < 0.01), and the BDNF content in the raphe nuclei was lower than in the model group (P < 0.05). There were no significant differences in tPA and BDNF mRNA between the EA and model groups.
CONCLUSION
EA may reverse depressive-like behaviors in CUMS, which may be related to the tPA/BDNF pathway in the hippocampus.
目的
采用慢性不可预测轻度应激（CUMS）大鼠模型，研究电针（EA）对组织型纤溶酶原激活剂（tPA）/脑源性神经营养因子（BDNF）通路的影响。
方法
将60只雄性Sprague-Dawley大鼠随机分为四组：正常组、模型组、氟西汀（fluox）组或电针组。对实验组进行28天的CUMS建模。在CUMS后1小时，氟西汀组和电针组分别给予氟西汀和20分钟的电针干预。通过旷场试验和蔗糖偏好试验评估抑郁样行为。大鼠处死后，取脑并进行苏木精-伊红（HE）染色，观察海马3区神经元的形态和数量变化。蛋白质免疫印迹法（Western blot）和实时聚合酶链反应（PCR）检测电针对海马和中缝核中tPA/BDNF通路相关分子的影响。
结果
与模型组相比，电针组的水平和垂直运动次数以及蔗糖消耗百分比显著增加（P<0.01）。与模型组相比，HE染色显示电针组和氟西汀组海马神经元排列整齐，层次丰富，细胞结构完整。蛋白质免疫印迹法和实时PCR结果显示，电针组海马中tPA、BDNF、原肌球蛋白受体激酶B（tropomyosin receptor kinase B）和BDNF微小RNA（mRNA）水平高于模型组（分别为P<0.01、P<0.01、P<0.05、P<0.01）。电针组海马中p75神经营养因子受体（p75NTR）、前体BDNF和tPA mRNA含量与模型组相比无显著差异。电针组中缝核tPA mRNA含量高于模型组（P<0.01），中缝核BDNF含量低于模型组（P<0.05）。电针组与模型组tPA和BDNF mRNA无显著差异。
结论
电针可能逆转CUMS诱导的抑郁样行为，这可能与海马中的tPA/BDNF通路有关。
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