Electroacupuncture ameliorates cognitive impairment through inhibition of NF-κB-mediated neuronal cell apoptosis in cerebral ischemia-reperfusion injured rats

Electroacupuncture ameliorates cognitive impairment through inhibition of NF-κB-mediated neuronal cell apoptosis in cerebral ischemia-reperfusion injured rats
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DOI:
10.3892/mmr.2013.1392
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发表时间:
2013-05-01
影响因子:
3.4
通讯作者:
Chen, Lidian
Chen, Lidian
中科院分区:
医学4区
文献类型:
--
作者:
Feng, Xiaodong;Yang, Shanli;Chen, Lidian

文献摘要

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认知障碍是脑卒中后严重的精神缺陷,严重影响脑卒中幸存者的生活质量。核因子-κ B(NF-kappa B)介导的神经元细胞凋亡参与了脑卒中后认知功能障碍的发生发展,已成为治疗脑卒中后认知功能障碍的有效靶点。在中国,针灸百会(DU 20)和神庭(DU 24)穴位是临床上常用的治疗中风后认知障碍的方法;然而,其确切的作用机制在很大程度上尚不清楚。本研究采用大鼠局灶性脑缺血再灌注(I/R)损伤模型,观察电针治疗脑卒中后认知功能障碍的疗效,并探讨其分子机制。电针百会穴和神庭穴可明显改善神经功能缺损,减少脑梗死体积。此外,电针还能改善脑I/R损伤大鼠的学习记忆能力,对脑卒中后认知功能障碍有一定的治疗作用。电针可显著抑制缺血再灌注诱导的NF-κ B B信号通路的激活。电针对NF-κ B B活化的抑制作用可导致脑细胞凋亡的抑制。最后,电针显著下调促凋亡基因Bax和Fas的表达,这两个基因是NF-κ B通路的关键下游靶基因。总之,我们的研究结果表明,抑制NF-κ B介导的神经元细胞凋亡可能是电针百会和神庭对脑卒中后认知障碍发挥治疗作用的机制之一。
Cognitive impairment is a serious mental deficit following stroke that severely affects the quality of life of stroke survivors. Nuclear factor-kappa B (NF-kappa B)-mediated neuronal cell apoptosis is involved in the development of post-stroke cognitive impairment; therefore, it has become a promising target for the treatment of impaired cognition. Acupuncture at the Baihui (DU20) and Shenting (DU24) acupoints is commonly used in China to clinically treat post-stroke cognitive impairment; however, the precise mechanism of its action is largely unknown. In the present study, we evaluated the therapeutic efficacy of electroacupuncture against post-stroke cognitive impairment and investigated the underlying molecular mechanisms using a rat model of focal cerebral ischemia-reperfusion (I/R) injury. Electroacupuncture at Baihui and Shenting was identified to significantly ameliorate neurological deficits and reduce cerebral infarct volume. Additionally, electroacupuncture improved learning and memory ability in cerebral I/R injured rats, demonstrating its therapeutic efficacy against post-stroke cognitive impairment. Furthermore, electroacupuncture significantly suppressed the I/R-induced activation of NF-kappa B signaling in ischemic cerebral tissues. The inhibitory effect of electroacupuncture on NF-kappa B activation led to the inhibition of cerebral cell apoptosis. Finally, electroacupuncture markedly downregulated the expression of pro-apoptotic Bax and Fas, two critical downstream target genes of the NF-kappa B pathway. Collectively, our findings suggest that inhibition of NF-kappa B-mediated neuronal cell apoptosis may be one mechanism via which electroacupuncture at Baihui and Shenting exerts a therapeutic effect on post-stroke cognitive impairment.