血管性痴呆（vascular dementia，VaD）是仅次于阿尔茨海默病的第2大常见痴呆类型，其发病机制与慢性脑缺血、神经炎症及神经元凋亡密切相关。近年来的研究表明，内质网应激（endoplasmic reticulum stress，ERS）在VaD病理进程中扮演关键角色。脑缺血缺氧可导致未折叠和（或）错误折叠蛋白在内质网腔内积聚，触发未折叠蛋白反应（unfolded protein response，UPR）。持续的ERS通过过度激活蛋白激酶RNA样内质网激酶（protein kinase RNA-like endoplasmic reticulum kinase，PERK）-真核翻译启动因子2A（eukaryotic translation initiation factor 2A，eIF2α）-激活转录因子（activating transcription factor，ATF）4-氨基酸代谢基因以及促凋亡因子（C/EBP homologous protein，CHOP）、肌醇需要酶1（inositol-requiring enzyme 1，IRE1）α-IRE1-X-框结合蛋白1（X-box binding protein 1，XBP1）以及ATF6等核心信号通路，最终诱导神经元凋亡。本文综述了ERS在VaD中的作用机制，并重点探讨了中医药防治VaD的潜在策略。研究表明，多种中药复方（如桃红四物汤和补阳还五汤等）及中药提取物（如西红花苷和二苯乙烯苷等）能够通过多靶点、多通路协同作用，有效抑制ERS，减轻氧化应激反应与神经炎症，减少神经元凋亡，从而改善认知功能。靶向调控ERS为VaD治疗提供了新方向，深入研究中医药通过ERS途径防治VaD的具体分子机制，具有重要的理论价值和临床转化前景。

Vascular dementia (VaD) is the second most common type of dementia after Alzheimer's disease, and its pathogenesis is closely related to chronic cerebral ischemia, neuroinflammation, and neuronal apoptosis. Recent studies have indicated that endoplasmic reticulum stress (ERS) plays a critical role in the pathological process of VaD. Cerebral ischemia and hypoxia can lead to the accumulation of unfolded/misfolded proteins in the endoplasmic reticulum lumen, triggering the unfolded protein response (UPR). Persistent ERS excessively activates core signaling pathways such as protein kinase RNA-like endoplasmic reticulum kinase (PERK)-eukaryotic translation initiation factor 2A (eIF2α)-activating transcription factor (ATF)4-C/EBP homologous protein (CHOP), inositol-requiring enzyme 1 (IRE1)α-X-box binding protein 1 (XBP1), and ATF6, ultimately inducing neuronal apoptosis. This article reviews the mechanism of ERS in VaD and focuses on the potential strategies of traditional Chinese medicine (TCM) for preventing and treating VaD. Research has shown that various TCM compound formulations (e.g., Taohong Siwu Decoction, and Buyang Huanwu Decoction) and TCM extracts (e.g., crocin, and tetrahydroxystilbene glucoside) can effectively inhibit ERS through multi-target and multi-pathway synergistic effects, alleviate oxidative stress and neuroinflammation, reduce neuronal apoptosis, and thereby improve cognitive function. Targeting the regulation of ERS provides a new direction for VaD treatment. In-depth research into the specific molecular mechanisms of TCM in preventing and treating VaD via the ERS pathway holds significant theoretical value and clinical translation prospects.