Zhang Guofang, Hu Xiaolin, Qian Jun, Shi Yumei, Ling Zeng, Xu Ping, Xu Zucai, Zhang Jun, Liang Tao
Department of Neurology, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, China.
Department of Geriatrics, People's Hospital of Qianxinan Prefecture, 562400, Guizhou Province, China.
Sci Rep. 2025 Jun 3;15(1):19397. doi: 10.1038/s41598-025-04863-y.
Cerebrovascular diseases, particularly ischemic stroke, are a leading cause of global disability. Effective management of ischemia-reperfusion injury is crucial in stroke treatment. Emodin, known for its anti-inflammatory and neuroprotective properties, has been shown to protect against ischemia-reperfusion injury by modulating pyroptosis. However, the molecular mechanisms underlying its effects in cerebral ischemia-reperfusion injury are not well understood. This study aims to investigate the neuroprotective mechanisms of Emodin in ischemic stroke. SD rats were randomly assigned to different groups: control, sham, model, and Emodin intervention groups with varying dosages. Cerebral ischemia-reperfusion injury was induced using the middle cerebral artery occlusion (MCAO) method, and Emodin (10 mg/kg, 20 mg/kg, 40 mg/kg) was administered intraperitoneally. Neurological deficits were evaluated using the modified Neurological Severity Score (mNSS), and infarct volume was assessed via TTC staining. Pathomorphological changes were observed using HE staining. Protein expression levels associated with pyroptosis, including NLRP3, Caspase 1, and GSDMD, were analyzed by Western blotting and immunofluorescence. The levels of IL-1β and IL-18 were measured using ELISA (Caspase 1 indicates cleaved Caspase 1, GSDMD indicates the active pro-forms of GSDMD, used throughout). Emodin exhibits significant beneficial effects in improving neurological deficits caused by cerebral ischemia-reperfusion injury. It effectively reduces the ratio of infarct volume, alleviates cytopathic damage, and suppresses the expression of pyroptosis-related proteins, including NLRP3, Caspase 1, Caspase 1, and GSDMD. Furthermore, Emodin decreases the levels of pro-inflammatory cytokines IL-1β and IL-18, thus attenuating the inflammatory response. The expression of pyroptosis-related proteins is upregulated in rats after cerebral ischemia-reperfusion injury. Emodin demonstrates neuroprotective effects against cerebral ischemia-reperfusion injury in rats, potentially by modulating the expression of pyroptosis-related proteins mediated through the Caspase 1-GSDMD axis.
脑血管疾病，尤其是缺血性中风，是导致全球残疾的主要原因。有效管理缺血再灌注损伤在中风治疗中至关重要。大黄素以其抗炎和神经保护特性而闻名，已被证明可通过调节细胞焦亡来预防缺血再灌注损伤。然而，其在脑缺血再灌注损伤中的作用分子机制尚不完全清楚。本研究旨在探讨大黄素在缺血性中风中的神经保护机制。将SD大鼠随机分为不同组：对照组、假手术组、模型组和不同剂量的大黄素干预组。采用大脑中动脉闭塞（MCAO）法诱导脑缺血再灌注损伤，并腹腔注射大黄素（10mg/kg、20mg/kg、40mg/kg）。使用改良神经功能缺损评分（mNSS）评估神经功能缺损，通过TTC染色评估梗死体积。使用HE染色观察病理形态学变化。通过蛋白质印迹法和免疫荧光分析与细胞焦亡相关的蛋白质表达水平，包括NLRP3、半胱天冬酶1（Caspase 1）和Gasdermin D（GSDMD）。使用酶联免疫吸附测定法（ELISA）测量白细胞介素-1β（IL-1β）和白细胞介素-18（IL-18）的水平（Caspase 1表示裂解的Caspase 1，GSDMD表示活性前体形式的GSDMD，全文均使用此表述）。大黄素在改善脑缺血再灌注损伤引起的神经功能缺损方面具有显著的有益作用。它有效降低梗死体积比例，减轻细胞病变损伤，并抑制与细胞焦亡相关的蛋白质表达，包括NLRP3、Caspase 1、Caspase 1和GSDMD。此外，大黄素降低促炎细胞因子IL-1β和IL-18的水平，从而减轻炎症反应。脑缺血再灌注损伤大鼠中与细胞焦亡相关的蛋白质表达上调。大黄素对大鼠脑缺血再灌注损伤具有神经保护作用，可能是通过调节由Caspase 1-GSDMD轴介导的细胞焦亡相关蛋白质的表达来实现的。
