纸质出版日期:2024-07-20,
收稿日期:2024-04-22,
录用日期:2024-06-13
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BDNF/TrkB信号通路作为神经元生长、发育和突触可塑性的关键调节器,广泛参与中枢神经系统疾病的发生发展,如缺血性脑卒中、阿尔茨海默病、帕金森病和脊髓损伤等。研究表明针刺能调节BDNF/TrkB信号通路的活性,对以上疾病具有显著的治疗潜力,其作用机制与参与突触结构重塑,抑制神经细胞凋亡,促进神经发生和突触再生等有关。本文综述了BDNF/TrkB相关信号通路在中枢神经系统疾病中的作用以及针刺对该通路的调控机制,以期为临床治疗提供新思路。未来研究应深入探究针刺对BDNF/TrkB信号通路的精准调控,以开发更高效安全的治疗策略。
As a key regulator of neuronal growth, development and synaptic plasticity, BDNF/ TrkB signaling pathway is widely involved in the occurrence and development of central nervous system diseases, such as ischemic stroke, Alzheimer's disease, Parkinson's disease and spinal cord injury. Studies have shown that acupuncture can regulate the activity of BDNF/TrkB signaling pathway, and has significant therapeutic potential for these diseases. Its mechanism of action is related to participating in synaptic remodeling, inhibiting neuronal apoptosis, and promoting neurogenesis or synaptic regeneration. This article reviews the role of BDNF/TrkB signaling pathway in central nervous system diseases and the regulation mechanism of acupuncture on this pathway, in order to provide new ideas for clinical treatment. Future studies should further explore the precise regulatory mechanism of acupuncture on BDNF/TrkB signaling pathway in order to develop more efficient and safe treatment strategies.
中枢神经系统疾病是严重威胁人类健康的重大疾病之一,包括缺血性脑卒中(ischemic stroke, IS)、阿尔茨海默病(Alzheimer’s disease, AD)、帕金森(Parkinson’s disease, PD)和脊髓损伤(spinal cord injury, SCI)等。这些疾病常常伴随着神经元损伤、神经炎症、突触功能失调等复杂的病理生理变化,给患者的生活质量和健康带来了严重的影响[
BDNF是一种多肽神经营养因子,其结构包括一个亲水性氨基端(N端)和一个疏水性羧基端(C端),C端的成熟活性结构域可与TrkB受体结合,从而介导了BDNF的生物学效应[
TrkB位于神经细胞膜上,是由胞浆区域、跨膜区域和胞外区域组成的一种跨膜蛋白。作为BDNF的特异性受体,TrkB参与调节神经元的存活、发育、突触可塑性和学习记忆等过程[
PLC-γ是细胞信号传导的重要介质,能够催化磷脂酰肌醇二磷酸水解,产生IP3和二酰甘油。IP3可与其细胞内受体结合,诱导内质网配体门控的Ca2+通道开放,使细胞外的Ca2+进入细胞[
PI3K在BDNF与其特异性受体TrKB结合后被激活,然后催化细胞膜上的磷脂酰肌醇二磷酸转化为磷脂酰肌醇三磷酸,使Akt磷酸化并被激活[
BDNF与TrKB结合后还可激活MAPK级联反应。MAPK家族包括多个亚型,其中最常见的有细胞外调节蛋白激酶(extracellular signal-regulated kinase, ERK)、c-Jun N-末端激酶(c-Jun N-terminal Kinase, JNK)和p38丝裂原激活蛋白激酶(p38 mitogen activated protein kinases, p38MAPK),它们分别参与调节不同的细胞信号传导途径[
IS仍然是导致全球死亡和残疾的主要原因之一。IS发生后,BDNF/TrkB信号通路通过调控神经细胞凋亡、提高突触可塑性等机制发挥重要的神经保护作用[
针刺作为中医疗法的重要组成部分,在治疗IS方面展现出多途径多靶点的特点。研究[
AD占全部痴呆类型的60%~80%,其特征性标志为β-淀粉样蛋白(amyloid β-protein, Aβ)沉积形成的老年斑和神经细胞内高度磷酸化的微管相关蛋白(tubulin-associated unit, tau)错误折叠引起的神经纤维缠结[
针刺作为非药物治疗的中医传统疗法,根据其病因病机辨证论治,可明显改善AD认知功能,减少并发症发生,且具有安全性高,不良反应少等优势。近年来,针刺治疗AD的作用机制成为了研究热点,针刺可通过调控脑内蛋白表达、改善突触可塑性、调控线粒体自噬、调控小胶质细胞的生理病理状态、抑制神经细胞凋亡、调节脑区能量代谢等途径改善AD[
PD在人群中的发病率逐年上升,是仅次于AD之后的第二大神经退行性疾病。PD主要侵犯人的大脑黑质区域,导致多巴胺能神经元(dopamine, DA)变性丢失和路易小体的形成,其中α-突触核蛋白(α-Synuclein, α-Syn)是路易小体的主要构成部分[
中医学认为PD归属于“颤证”范畴,针刺可以通过激活BDNF/TrKB信号通路,有助于抑制黑质多巴胺能神经元的凋亡过程,并减轻神经炎症,从而改善PD运动及非运动症状,包括减少肌肉僵硬、增强运动协调能力以及缓解焦虑和抑郁等心理症状。Lin等[
SCI是临床常见较严重的中枢神经系统损伤,由于脊髓神经元再生困难,因此促进神经元生长存活、减少继发性损伤和促进脊髓轴突的修复等是治疗SCI的关键,而BDNF/TrKB信号通路在该过程中起到不可或缺的作用。研究[
中医学中SCI属于“体惰”“痿证”之症,而督脉瘀阻,气血运化失司是SCI的中医病理病机。针刺可以通过激活BDNF/TrkB信号通路促进受损神经元再生,提高突触可塑性,治疗SCI。早期研究[
综上所述,BDNF/TrkB信号通路在中枢神经系统疾病中的作用已经得到了广泛的关注,该信号通路的激活对多种中枢神经系统疾病的发生和发展具有重要的影响。针刺作为一种传统的治疗方法,通过调节BDNF/TrkB信号通路,参与突触结构重塑,促进神经发生和突触再生,抑制炎症反应等在中枢神经系统疾病的临床症状和预后方面显示出一定的潜力和疗效。然而,当前仍存在一些挑战需要面对和解决。首先,尽管我们已经初步了解了针刺对BDNF/TrkB信号通路的调控作用,但其具体的作用机制非常复杂。BDNF/TrkB信号通路参与了多种细胞信号转导途径,而针刺可能通过多种途径影响该信号通路的活性,因此需要深入研究其具体的作用机制。其次,针刺对BDNF/TrkB信号通路的调控并不局限于本文所回顾的这几种神经系统疾病,未来学者们可以继续探究针刺通过该信号通路对更多神经系统疾病的影响。最后,当前有关针刺调控BDNF/TrKB信号传导的研究大多数仍为动物实验研究,因此今后应积极开展相关临床研究,为中枢神经系统疾病的治疗提供新靶点。在未来的研究中,我们还应该关注如何结合传统医学和现代医学的优势,进一步探索针刺对BDNF/TrkB信号通路的精准调控机制,从而为中枢神经系统疾病的治疗开发出更加有效的新型治疗策略。
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