Sun Pei-Yang, Chu Hao-Ran, Li Nan, Liu Hui, Liu Shi-Yang, Zhang Fang, Li Wei, Chu Shui-Rou, Li Pei-Fang
Department of Encephalopathy, Second Affiliated Hospital of Anhui University of CM, Hefei 230061, China.
Graduate School of Anhui University of CM.
Zhongguo Zhen Jiu. 2022 Aug 12;42(8):907-13. doi: 10.13703/j.0255-2930.20220206-k0003.
To observe the regulative effect of acupuncture on the depression-like behavior and cAMP-response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF)/tyrosine protein kinase B (TrkB) signaling pathway of hippocampus in rats with post-stroke depression (PSD), and to explore its possible mechanism on improving PSD.
A total of 36 SPF SD rats were randomized into a sham operation group, a model group and a Tongdu Tiaoshen group, 12 rats in each group. The compound method of Zea Longa suture-occlusion and chronic unpredictable mild stress (CUMS) was used to establish the PSD model in rats of the model group and the Tongdu Tiaoshen group. On the 4th day after modeling, acupuncture was applied at "Dazhui" (GV 14), "Shuigou" (GV 26), "Baihui" (GV 20) and "Shenting" (GV 24) in the Tongdu Tiaoshen group, 40 min every time, once a day, 6 times a week for 4 weeks consecutively. On the 2nd day after PSD modeling and after 4-week intervention, Zea Longa neurobehavioral score was evaluated, sucrose water consumption test and open-field test were performed; biochemical method was used to detect the SOD, CAT activity and MDA level in hippocampal CA1 area; ELISA method was used to detect the serum level of BDNF; real-time PCR was used to detect the mRNA expression of BDNF, TrkB and CREB in hippocampal CA1 area; Western blot was used to detect the protein expression of BDNF, TrkB, CREB and p-CREB in hippocampal CA1 area.
Compared with the sham operation group, Zea Longa neurobehavioral scores were increased (<0.05), percentage of sucrose water consumption, horizontal motion and vertical motion scores of open-field test were decreased after modeling and intervention in the model group and after modeling in the Tongdu Tiaoshen group (<0.05). Compared with the model group, Zea Longa neurobehavioral score was decreased (<0.05), percentage of sucrose water consumption, horizontal motion and vertical motion scores of open-field test were increased after intervention in the Tongdu Tiaoshen group (<0.05). Compared with the sham operation group, the SOD and CAT activity in hippocampal CA1 area and serum level of BDNF were decreased (<0.05), MDA level in hippocampal CA1 area was increased in the model group (<0.05); compared with the model group, the SOD and CAT activity in hippocampal CA1 area and serum level of BDNF were increased (<0.05), MDA level was decreased in the Tongdu Tiaoshen group (<0.05). Compared with the sham operation group, the mRNA expression of BDNF, TrkB and CREB as well as the protein expression of BDNF, TrkB, CREB and p-CREB were decreased in hippocampal CA1 area in the model group (<0.05); compared with the model group, the mRNA expression of BDNF, TrkB and CREB, the protein expression of BDNF, TrkB and p-CREB as well as the ratio of p-CREB/CREB were increased in the Tongdu Tiaoshen group (<0.05).
acupuncture can improve the depression-like behavior in PSD rats, the mechanism may be related to the inhibition of oxidative stress in hippocampal tissues and the enhanced activity of CREB/BDNF/TrkB signaling pathway.
观察针刺对脑卒中后抑郁(PSD)大鼠抑郁样行为及海马环磷腺苷反应元件结合蛋白(CREB)/脑源性神经营养因子(BDNF)/酪氨酸蛋白激酶B(TrkB)信号通路的调节作用,探讨其改善PSD的可能机制。
将36只SPF级SD大鼠随机分为假手术组、模型组和通督调神组,每组12只。采用线栓法结合慢性不可预知温和应激(CUMS)复合方法建立模型组和通督调神组大鼠PSD模型。造模后第4天,通督调神组大鼠针刺“大椎”(GV 14)、“水沟”(GV 26)、“百会”(GV 20)、“神庭”(GV 24),每次40分钟,每天1次,每周6次,连续4周。在PSD造模后第2天及干预4周后,评估线栓法神经行为学评分,进行糖水消耗试验和旷场试验;采用生化方法检测海马CA1区超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性及丙二醛(MDA)水平;采用酶联免疫吸附测定(ELISA)法检测血清BDNF水平;采用实时荧光定量聚合酶链反应(real-time PCR)检测海马CA1区BDNF、TrkB和CREB的mRNA表达;采用蛋白质免疫印迹法(Western blot)检测海马CA1区BDNF、TrkB、CREB和磷酸化CREB(p-CREB)的蛋白表达。
与假手术组比较,模型组造模及干预后、通督调神组造模后线栓法神经行为学评分升高(<0.05),糖水消耗百分比、旷场试验水平运动和垂直运动评分降低(<0.05)。与模型组比较,通督调神组干预后线栓法神经行为学评分降低(<0.05),糖水消耗百分比、旷场试验水平运动和垂直运动评分升高(<0.05)。与假手术组比较,模型组海马CA1区SOD、CAT活性及血清BDNF水平降低(<0.05),海马CA1区MDA水平升高(<0.05);与模型组比较,通督调神组海马CA1区SOD、CAT活性及血清BDNF水平升高(<0.05),MDA水平降低(<0.05)。与假手术组比较,模型组海马CA1区BDNF、TrkB和CREB的mRNA表达以及BDNF、TrkB、CREB和p-CREB的蛋白表达降低(<0.05);与模型组比较,通督调神组海马CA1区BDNF、TrkB和CREB的mRNA表达,BDNF、TrkB和p-CREB的蛋白表达以及p-CREB/CREB比值升高(<0.05)。
针刺可改善PSD大鼠的抑郁样行为,其机制可能与抑制海马组织氧化应激及增强CREB/BDNF/TrkB信号通路活性有关。