中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2025, Vol. 20 ›› Issue (10): 2758-2775.doi: 10.4103/NRR.NRR-D-24-00568

• 综述:脑损伤修复保护与再生 • 上一篇    下一篇

缺血性脑卒中的PI3K/AKT信号转导和神经保护：分子机制和治疗前景

  

  • 出版日期:2025-10-15 发布日期:2025-02-07

PI3K/AKT signaling and neuroprotection in ischemic stroke: molecular mechanisms and therapeutic perspectives

Tianlong Liu1, 2, #, Xiaolin Li2, #, Xiaowei Zhou3 , Wei Chen3 , Aidong Wen1 , Minna Liu4, *, Yi Ding1, *   

  1. 1 Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi Province, China;  2 Department of Pharmacy, The 940 Hospital of Joint Logistics Support Forces of Chinese PLA, Lanzhou, Gansu Province, China;  3 Department of Pharmacy, The 944 Hospital of Joint Logistics Support Forces of Chinese PLA, Jiuquan, Gansu Province, China;  4 Department of Nephrology, The 940 Hospital of Joint Logistics Support Forces of Chinese PLA, Lanzhou, Gansu Province, China
  • Online:2025-10-15 Published:2025-02-07
  • Contact: Yi Ding, PhD, dingyi.007@163.com; Minna Liu, MD, lmn2010@foxmail.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 82274313 (to YD), 82204746 (to ML), 82003982 (to TL)

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摘要：

目前研究表明，PI3K/Akt信号通路缺血性脑卒中的发病机制起着关键作用，针对PI3K/Akt通路的药物开发也引起了研究人员的极大关注。为此，文章以PI3K/Akt通路为出发点，详细综述了缺血性脑卒中的病理机制和信号通路研究进展发现：①缺血性脑卒中复杂的病理机制归纳为5大类：兴奋性氨基酸毒性、钙超载、炎症反应、氧化应激和细胞凋亡。②PI3K/AKT介导的信号通路与缺血性脑卒中的发生和发展密切相关，主要为核转录因子κB信号通路、Nrf2信号通路、Bcl-2信号通路、mTOR信号通路和eNOS信号通路。③此外，天然产物来源丰富，包括黄酮类、醌类、生物碱类、苯丙类、酚类、萜类、虹彩类等，是开发创新型抗脑卒中药物的重要候选物质，应用前景广阔。④近年来，电针和间充质干细胞疗法等新技术疗法已显示出通过激活PI3K/Akt通路改善脑卒中预后的潜力，这为缺血性脑卒中的治疗和康复提供了新的可能性。⑤未来研究者们需要进一步加强PI3K/AKT药物的直接调控机制相关研究，促进临床转化，以期为缺血性脑卒中提供创新的治疗策略。

https://orcid.org/0000-0002-2158-3108 (Yi Ding); https://orcid.org/0000-0002-1566-6759 (Minna Liu) 

关键词: 细胞凋亡, 自噬, 炎症, 缺血性脑卒中, 神经保护, 氧化应激, 发病机制, 磷脂酰肌醇3-激酶, 蛋白激酶B, 治疗学

Abstract: It has been reported that the PI3K/AKT signaling pathway plays a key role in the pathogenesis of ischemic stroke. As a result, the development of drugs targeting the PI3K/AKT signaling pathway has attracted increasing attention from researchers. This article reviews the pathological mechanisms and advancements in research related to the signaling pathways in ischemic stroke, with a focus on the PI3K/AKT signaling pathway. The key findings include the following: (1) The complex pathological mechanisms of ischemic stroke can be categorized into five major types: excitatory amino acid toxicity, Ca2+ overload, inflammatory response, oxidative stress, and apoptosis. (2) The PI3K/AKTmediated signaling pathway is closely associated with the occurrence and progression of ischemic stroke, which primarily involves the NF-κB, NRF2, BCL-2, mTOR, and endothelial NOS signaling pathways. (3) Natural products, including flavonoids, quinones, alkaloids, phenylpropanoids, phenols, terpenoids, and iridoids, show great potential as candidate substances for the development of innovative anti-stroke medications. (4) Recently, novel therapeutic techniques, such as electroacupuncture and mesenchymal stem cell therapy, have demonstrated the potential to improve stroke outcomes by activating the PI3K/ AKT signaling pathway, providing new possibilities for the treatment and rehabilitation of patients with ischemic stroke. Future investigations should focus on the direct regulatory mechanisms of drugs targeting the PI3K/AKT signaling pathway and their clinical translation to develop innovative treatment strategies for ischemic stroke.

Key words: apoptosis, autophagy, inflammation, ischemic stroke, neuroprotection, oxidative stress, pathogenesis, phosphatidylinositol 3-kinase, protein kinase B, therapeutics