《生命科学》 2025, 37(3): 296-303
细胞焦亡在脑缺血再灌注损伤中作用机制的研究进展
摘 要：
脑缺血再灌注损伤是导致缺血性脑卒中等疾病的主要- 原因之一，再灌注过程中引发的氧化应激、炎症反应和细胞焦亡显著加剧了脑损伤。细胞焦亡由NLRP3 炎症小体激活，通过Caspase-1 介导裂解GSDMD 形成细胞膜孔道，释放IL-1β 和IL-18 等炎症因子，加重炎症反应和神经元死亡。本文综述了细胞焦亡在脑缺血再灌注损伤中的作用机制，讨论了通过抑制NLRP3、Caspase-1 和GSDMD 的活性来调控细胞焦亡的潜在治疗方法，包括小分子抑制剂和天然产物。此外，多靶点联合治疗，如抗炎和抗氧化剂的联合疗法也展现出显著的潜力。进一步优化这些抑制剂的特异性和功能，并探索多功能纳米载体和基因编辑技术，以实现多重病理机制的干预，提高治疗效果。
通讯作者：蒋希成 , Email:jiangxicheng5303@163.com
Abstract:
Cerebral ischemia-reperfusion injury is one of the main causes of ischemic stroke and other diseases. Oxidative stress, inflammation and cell pyroptosis caused by reperfusion significantly aggravate brain injury. Pyroptosis, mediated by the activation of the NLRP3 inflammasome, involves Caspase-1-mediated cleavage of GSDMD to form cell membrane pores, resulting in the release of inflammatory cytokines such as IL-1β and IL-18, which further intensify inflammation and neuronal death. This review summarizes the mechanisms of pyroptosis in cerebral ischemia-reperfusion injury and discusses potential therapeutic strategies to regulate pyroptosis by inhibiting the activity of NLRP3, Caspase-1, and GSDMD, including the use of small molecule inhibitors and natural products. Additionally, multi-target combination therapies, such as the combined use of anti-inflammatory and antioxidant agents, have shown significant therapeutic potential. Future research should focus on optimizing the specificity and functionality of these inhibitors and exploring the development of multifunctional nanocarriers and gene-editing technologies to achieve intervention in multiple pathological mechanisms, thereby enhancing therapeutic efficacy.
Communication Author：JIANG Xi-Cheng , Email:jiangxicheng5303@163.com
