目的 探讨金银花-连翘药对改善川崎病小鼠血管炎的作用及机制。方法 将 C57BL/6 小鼠随机分为正 常组（5 只）、模型组（6 只）和中药组（5 只）。采用腹腔注射 0.2 mL 白色念珠菌水溶物（20 mg·mL-1 ）复制川崎病 小鼠模型，每日 1 次，连续 5 d。模型复制的同时，中药组小鼠给予金银花-连翘提取物（生药量 2.6 g·kg-1 ）灌 胃，正常组、模型组灌胃等量 PBS。末次注射后，继续喂养 14 d，然后取样进行后续实验。采用 HE 及 EVG 染色法观察心脏组织病理变化；免疫荧光法检测心脏组织中 Ly6G、基质金属蛋白酶 9（MMP9）表达水平；细胞 因子检测试剂盒检测小鼠外周血中 40 种细胞因子的表达水平，并筛选差异表达细胞因子，进行 GO 功能及 KEGG 通路富集分析。结果 （1）与正常组比较，模型组小鼠心脏血管内皮粗糙，结构不完整，细胞排列无序， 血管及周围心肌组织可见炎性细胞广泛浸润；心脏血管壁弹力纤维排列紊乱，松散断裂；血管及周围心肌组织 中可见大量中性粒细胞广泛浸润，Ly6G 表达显著上调（P＜0.01）；心脏组织中 MMP9 蛋白表达显著上调（P＜ 0.01）。与模型组比较，中药组小鼠心脏血管内皮结构较完整，炎性细胞浸润减轻；心脏血管壁弹力纤维较规 整，未见明显断裂；心脏血管区域的中性粒细胞浸润明显减少，Ly6G 表达显著下调（P＜0.01）；心脏组织中 MMP9 蛋白表达显著下调（P＜0.01）。（2）与正常组比较，模型组有 28 个差异表达细胞因子，均显著上调（Padj＜ 0.05）；与模型组比较，中药组有 17 个差异表达细胞因子，其中 16 个显著下调（Padj＜0.05），1 个显著上调 （Padj＜0.05）。有 14 个差异表达细胞因子为正常组 vs 模型组的上调基因，而在金银花-连翘干预后显著回调。 差异表达细胞因子涉及白细胞迁移、细胞因子介导的信号通路、粒细胞趋化性等生物过程；涉及细胞因子活 性、细胞因子受体结合、趋化因子活性等分子功能；以及涉及趋化因子信号通路、TNF 信号通路、JAK-STAT 信号通路等相关通路。结论 金银花-连翘药对可改善川崎病小鼠的血管炎，其机制可能与减少中性粒细胞浸 润，下调 MMP9 表达，以及抑制外周相关血细胞因子表达有关。

Objective To explore the effect and mechanism of Lonicerae Japonicae Flos-Forsythiae Fructus on improving vasculitis in Kawasaki disease mouse model. Method C57BL/6 mice were randomly divided into the normal group （n = 5），model group （n = 6） and Chinese medicine group （n = 5）. The Kawasaki disease mouse model was replicated by intraperitoneal injection of 0.2 mL Candida albicans water soluble fraction （20 mg·mL-1 ） once a day for 5 days. At the same time of model replication， the mice in the Chinese medicine group were given Lonicerae Japonicae Flos-Forsythiae Fructus extract （crude drug 2.6 g·kg-1 ） by gavage，and the normal group and the model group were given the same amount of PBS by gavage. After the last injection，the rats were fed for 14 days，and then sampled for subsequent experiments. HE and EVG staining were used to observe the pathological changes of heart tissue. The expression levels of Ly6 G and MMP9 in heart tissue were detected by immunofluorescence. The cytokine assay kit was used to detect the expression levels of 40 cytokines in peripheral blood of mice，and the differentially expressed cytokines were screened for GO function and KEGG pathway enrichment analysis. Results （1） Compared with the normal group，the cardiac vascular endothelium of the model group was rough and the structure was incomplete，the cells were disorderly arranged，and the inflammatory cells were widely infiltrated in the blood vessels and surrounding myocardial tissues. Cardiac vascular wall elastic fibers arranged in disorder， loose fracture； a large number of neutrophils were widely infiltrated in the blood vessels and surrounding myocardial tissues，and the expression of Ly6 G was significantly up-regulated （P＜0.01）. The protein expression of MMP9 in heart tissue was significantly upregulated （P＜0.01） . Compared with the model group，the cardiac vascular endothelial structure of the mice in the Chinese medicine group was more complete，and the infiltration of inflammatory cells was reduced；the elastic fibers of the cardiac vascular wall were relatively regular and no obvious fracture was observed. The infiltration of neutrophils in the cardiac vascular area was significantly reduced，and the expression of Ly6 G was significantly down-regulated （P＜ 0.01） . The protein expression of MMP9 in heart tissue was significantly down-regulated （P＜0.01）. （2） Compared with the normal group，there were 28 differentially expressed cytokines in the model group，which were significantly up-regulated （Padj＜0.05）. Compared with the model group， there were 17 differentially expressed cytokines in the Chinese medicine group， of which 16 were significantly down-regulated （Padj＜0.05） and 1 was significantly upregulated （Padj＜0.05）. There were 14 differentially expressed cytokines as up-regulated genes in the normal group versus the model group， which were significantly reversed after Lonicerae Japonicae Flos-Forsythiae Fructus intervention. Differentially expressed cytokines are involved in biological processes such as leukocyte migration， cytokine-mediated signaling pathways， and granulocyte chemotaxis； molecular functions such as cytokine activity， cytokine receptor binding，and chemokine activity；and chemokine signaling pathway，TNF signaling pathway，JAKSTAT signaling pathway and other related pathways. Conclusion Lonicerae Japonicae Flos-Forsythiae Fructus can improve vasculitis in mice with Kawasaki disease， and its mechanism may be related to the reduction of neutrophil infiltration，down-regulation of MMP9 expression，and inhibition of peripheral blood cell factor expression.

R285.5

国家自然科学基金项目（82270529）；苏州市科技局科研项目（SKY2023191，SKYD2023216）；苏州市姑苏卫生人才计划项目 （GSWS2024093）