Page 120 - 《中国药科大学学报》2026年第2期

学报
246 Journal of China Pharmaceutical University 2026, 57(2): 246 − 255

吲哚布芬通过抑制 NF-κB/Caspase-1/GSDMD 通路减轻

脑缺血再灌注损伤的作用与机制研究

许译尹 ，徐 丹 ，勾 雪 ，方伟蓉 ，李运曼 ，邵 华 ，王永庆 1,5**
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（ 徐州医科大学药学院, 徐州 221004； 东南大学附属中大医院药学部, 南京 210009； 中国药科大学基础医学与临床药学学
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院, 南京 210009； 众红生物工程创药研究院有限公司, 常州 213000； 江苏省人民医院 (南京医科大学第一附属医院) 药学部,
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南京 210009）
摘 要 吲哚布芬作为新一代抗血小板药物，已在动物模型中表现出抗血栓作用，但其对脑缺血/再灌注（I/R）损伤的疗效
及机制尚待阐明。本研究通过大鼠大脑中动脉闭塞/再灌注（MCAO/R）模型，评估吲哚布芬预处理与后处理的神经保护作
用；利用人脐静脉内皮细胞（HUVECs）氧-糖剥夺/复氧（OGD/R）模型探究其体外保护机制，并初步探讨吲哚布芬与 NF-
κB/Caspase-1/GSDMD 介导的细胞焦亡通路的关系。药效学实验表明，吲哚布芬可显著降低 MCAO/R 大鼠血栓素
A 2 （TXA 2 ）代谢产物 TXB 2 水平、缩小脑梗死体积、减轻脑水肿及神经功能缺损，同时抑制 HUVECs 焦亡。机制研究表明，
其作用可能与通过调控 NF-κB/Caspase-1/GSDMD 通路抑制细胞焦亡相关。吲哚布芬通过下调 NF-κB/Caspase-1/GSDMD 通
路抑制细胞焦亡，从而对脑 I/R 损伤发挥保护和治疗作用。
关键词 吲哚布芬；缺血/再灌注损伤；细胞焦亡；NF-κB/Caspase-1/GSDMD 通路；人脐静脉内皮细胞
中图分类号 R965 文献标志码 A 文章编号 1000−5048(2026)02−0246−10
doi：10.11665/j.issn.1000−5048.2025091701

引用本文 许译尹，徐丹，勾雪，等. 吲哚布芬通过抑制 NF-κB/Caspase-1/GSDMD 通路减轻脑缺血再灌注损伤的作用与机制研究 [J]. 中国
药科大学学报，2026，57（2）：246-255.

Cite this article as: XU Yiyin, XU Dan, GOU Xue, et al. Indobufen attenuates cerebral ischemia–reperfusion injury by inhibiting the NF-
κB/Caspase-1/GSDMD pathway[J]. J China Pharm Univ, 2026, 57(2): 246-255.

Indobufen attenuates cerebral ischemia–reperfusion injury by inhibiting the
NF-κB/Caspase-1/GSDMD pathway

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XU Yiyin , XU Dan , GOU Xue , FANG Weirong , LI Yunman , SHAO Hua , WANG Yongqing 1,5**
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School of Pharmacy, Xuzhou Medical University, Xuzhou 221004; Department of Pharmacy, Zhongda Hospital, Southeast
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University, Nanjing 210009; School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing
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210009; Zonhon Biopharma Institute, Inc., Changzhou 213000; Department of Pharmacy, Jiangsu Provincial People's Hospital,
The First Affiliated Hospital of Nanjing Medical University, Nanjing 210009, China
Abstract Indobufen is a new generation of antiplatelet agents and has been shown to have antithrombotic
effects in animal models. However, its therapeutic potential and mechanisms against cerebral
ischemia/reperfusion (I/R) injury remain unclear. In this study, we evaluated the in vivo neuroprotective effects of
indobufen through both pretreatment and posttreatment regimens in a rat model of middle cerebral artery
occlusion/reperfusion (MCAO/R). In vitro, human umbilical vein endothelial cells (HUVECs) subjected to
oxygen-glucose deprivation/reoxygenation (OGD/R) were employed to investigate the relationship between
indobufen and the pyroptosis-associated NF-κB/Caspase-1/GSDMD pathway. The pharmacodynamic tests
revealed that indobufen ameliorated I/R injury by decreasing the level of thromboxane B (TXB ), infarct size,
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brain edema and neurological impairment in rats and rescuing cell pyroptosis in HUVECs. The underlying

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收稿日期 2025-09-17 通信作者 E-mail：gycsh@163.com
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E-mail：wyqjsph@163.cpm