目的 基于Wnt/β-连环蛋白（β-catenin）信号通路探讨黄芩苷对动脉粥样硬化（atherosclerosis，AS）大鼠模型炎症反应的影响。方法 SD大鼠随机分为对照组、模型组及黄芩苷低、中、高剂量（50、100、150 mg/kg）组和黄芩苷（150 mg/kg）＋β-catenin激动剂SKL2001（10 mg/kg）组，每组14只。通过喂养高脂饲料与ip维生素D₃的方法建立AS大鼠模型。给予药物干预4周后，采用苏木素-伊红（hematoxylin eosin，HE）染色观察各组大鼠胸主动脉组织病理学形态；油红O染色观察各组大鼠胸主动脉斑块变化；检测各组大鼠血脂、炎性因子和内皮细胞因子水平；Western blotting检测各组大鼠胸主动脉组织中Wnt5a、β-catenin、糖原合酶激酶-3β（glycogen synthase kinase-3β，GSK-3β）和p-GSK-3β蛋白表达。结果 与对照组比较，模型组大鼠AS斑块面积、血清中低密度脂蛋白胆固醇（low-density lipoprotein cholesterol，LDL-C）、三酰甘油（triglyceride，TG）、总胆固醇（total cholesterol，TC）、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、白细胞介素-6（interleukin-6，IL-6）、IL-1β、内皮素-1（endothelin-1，ET-1）、细胞间黏附分子-1（intercellular cell adhesion molecule-1，ICAM-1）水平及主动脉Wnt5a、β-catenin、p-GSK-3β蛋白表达水平明显升高（P＜0.05），血清中高密度脂蛋白胆固醇（high-density lipoprotein cholesterol，HDL-C）、一氧化氮（nitric oxide，NO）水平及主动脉GSK-3β蛋白表达水平明显降低（P＜0.05）；与模型组比较，黄芩苷低、中、高剂量组大鼠AS斑块面积、血清LDL-C、TG、TC、TNF-α、IL-6、IL-1β、ET-1、ICAM-1水平及主动脉Wnt5a、β-catenin、p-GSK3β蛋白表达水平明显降低（P＜0.05），血清中HDL-C、NO水平及主动脉GSK-3β蛋白表达水平明显升高（P＜0.05），且呈剂量相关性；SKL2001显著逆转黄芩苷对AS大鼠的作用（P＜0.05）。结论 黄芩苷可能通过抑制Wnt/β-catenin信号通路抑制AS大鼠模型炎症反应。

Objective To investigate the effect of baicalin on inflammation in atherosclerotic (AS) rat model based on Wnt/β-catenin signaling pathway.Methods SD rats were randomly divided into control group, model group, baicalin low-, medium-, high-dose (50, 100, 150 mg/kg) groups, and baicalin (150 mg/kg) + β-catenin agonist SKL2001 (10 mg/kg) group, with 14 rats in each group. An AS rat model was established by feeding high-fat diet and ip vitamin D₃. After four weeks of drug intervention, the pathological morphology of thoracic aorta tissue in each group of rats was observed using hematoxylin eosin (HE) staining; Oil red O staining was used to observe the changes in thoracic aortic plaques of rats in each group; Levels of blood lipids, inflammatory factors and endothelial cytokines in serum of rats in each group were detected; Western blotting was used to detect the protein expressions of Wnt5a, β-catenin, glycogen synthase kinase-3β (GSK-3β) and p-GSK-3β in thoracic aortic tissues of rats in each group. Results Compared with control group, AS plaque area, levels of low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), total cholesterol (TC), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, endothelin-1 (ET-1), intercellular adhesion molecule-1 (ICAM-1) in serum and protein expression levels of Wnt5a, β-catenin, p-GSK3β in aortic tissues of rats in model group were significantly increased (P < 0.05), while the levels of high density lipoprotein cholesterol (HDL-C), nitric oxide (NO) in serum and GSK-3β protein expression in aortic tissues were significantly decreased (P < 0.05). Compared with model group, AS plaque area, levels of LDL-C, TG, TC, TNF-α, IL-6, IL-1β, ET-1, ICAM-1 in serum and protein expression levels of Wnt5a, β-catenin, p-GSK3β in aortic tissues of rats in baicalin low-, medium- and high-dose groups were significantly decreased (P < 0.05), levels of HDL-C, NO in serum and GSK-3β protein expression in aortic tissues were significantly increased (P < 0.05), with a dose-dependent manner. SKL2001 significantly reversed the effect of baicalin on AS rats (P < 0.05). Conclusion Baicalin may inhibit the inflammatory response of AS rats model by down-regulating Wnt/β-catenin signaling pathway.

R285.5

江西省卫生健康委科技计划项目（202130277）