目的 探讨铜过载介导的内质网应激（endoplasmic reticulum stress, ERS）在川崎病（Kawasaki disease, KD）血管内皮损伤中的作用及机制。 方法 将4周龄雄性C57BL/6小鼠随机分为对照组、KD组、KD+铜螯合剂四硫代钼酸盐（tetrathiomolybdate, TTM）组及KD+内质网应激抑制剂AMG PERK 44（AMG）组（每组n=20），使用白色念珠菌提取物构建KD小鼠模型；将人脐静脉内皮细胞（human umbilical vein endothelial cell, HUVEC）分为对照组（健康儿童血清干预）、KD组（KD患儿血清干预）、KD+TTM组（KD患儿血清联合20 μmol/L TTM干预）。采用红氨酸铜染色检测小鼠心脏组织铜沉积情况，通过测量小鼠腹主动脉直径和面积、苏木精-伊红染色观察小鼠血管病理改变，透射电镜、免疫荧光检测ERS激活情况；采用CCK8、流式细胞术、细胞划痕和细胞成管实验评估HUVEC细胞活力、凋亡和功能改变，Western blot法检测ERS标志蛋白表达水平。 结果 与KD组比较，KD+TTM组和KD+AMG组血管壁铜盐沉积减少，冠状动脉内皮细胞和内质网肿胀、炎性细胞浸润、腹主动脉病变扩张减轻；腹主动脉直径和面积、ERS标志蛋白（GRP78、CHOP）荧光强度降低（P<0.05）。与KD组比较，KD+TTM组细胞活力、小管数目、划痕愈合率升高，细胞凋亡率、ERS标志蛋白（GRP78、CHOP、ATF6和p-PERK）表达降低（P<0.05）。 结论 铜过载通过激活ERS通路加重KD血管内皮损伤，TTM可通过调控铜代谢及抑制ERS通路发挥内皮保护作用。

Objective To investigate the role and mechanism of copper overload-mediated endoplasmic reticulum stress (ERS) in vascular endothelial injury in Kawasaki disease (KD). Methods Four-week-old male C57BL/6 mice were randomly divided into four groups: control, KD, KD plus copper chelator tetrathiomolybdate (TTM), and KD plus ERS inhibitor AMG PERK 44 (AMG) (n=20 per group). A KD mouse model was established using Candida albicans extract. Human umbilical vein endothelial cells (HUVECs) were divided into control (intervention with healthy children's serum), KD (intervention with KD patients' serum), and KD+TTM (intervention with KD patients' serum plus 20 µmol/L TTM). Copper deposition in mouse heart tissue was assessed using rubeanic acid staining. Vascular pathological changes were observed using hematoxylin-eosin staining and measurement of abdominal aortic diameter and area. ERS activation was detected by transmission electron microscopy and immunofluorescence. HUVEC viability, apoptosis, and functional changes were evaluated using CCK8, flow cytometry, cell scratch assay, and angiogenesis experiments. ERS marker protein expression levels were measured by Western blot. Results Compared to the KD group, the KD+TTM and KD+AMG groups showed reduced copper deposition in the vascular wall, decreased swelling of coronary endothelial cells and endoplasmic reticulum, reduced inflammatory cell infiltration, and less abdominal aortic lesion expansion. The abdominal aortic diameter and area, and the fluorescence intensity of ERS marker proteins (GRP78 and CHOP) were significantly lower (P<0.05). Compared to the KD group, the KD+TTM group exhibited increased cell viability, tube number, and scratch healing rate, along with decreased apoptosis rate and expression of ERS marker proteins (GRP78, CHOP, ATF6, and p-PERK) (P<0.05). Conclusions Copper overload aggravates vascular endothelial injury in KD by activating the ERS pathway. TTM can exert protective effects on the endothelium by regulating copper metabolism and inhibiting the ERS pathway.