目的 基于Wnt/β-連環(huán)蛋白（β-catenin）信號通路探討黃芩苷對動脈粥樣硬化（atherosclerosis，AS）大鼠模型炎癥反應(yīng)的影響。方法 SD大鼠隨機(jī)分為對照組、模型組及黃芩苷低、中、高劑量（50、100、150 mg/kg）組和黃芩苷（150 mg/kg）＋β-catenin激動劑SKL2001（10 mg/kg）組，每組14只。通過喂養(yǎng)高脂飼料與ip維生素D₃的方法建立AS大鼠模型。給予藥物干預(yù)4周后，采用蘇木素-伊紅（hematoxylin eosin，HE）染色觀察各組大鼠胸主動脈組織病理學(xué)形態(tài)；油紅O染色觀察各組大鼠胸主動脈斑塊變化；檢測各組大鼠血脂、炎性因子和內(nèi)皮細(xì)胞因子水平；Western blotting檢測各組大鼠胸主動脈組織中Wnt5a、β-catenin、糖原合酶激酶-3β（glycogen synthase kinase-3β，GSK-3β）和p-GSK-3β蛋白表達(dá)。結(jié)果 與對照組比較，模型組大鼠AS斑塊面積、血清中低密度脂蛋白膽固醇（low-density lipoprotein cholesterol，LDL-C）、三酰甘油（triglyceride，TG）、總膽固醇（total cholesterol，TC）、腫瘤壞死因子-α（tumor necrosis factor-α，TNF-α）、白細(xì)胞介素-6（interleukin-6，IL-6）、IL-1β、內(nèi)皮素-1（endothelin-1，ET-1）、細(xì)胞間黏附分子-1（intercellular cell adhesion molecule-1，ICAM-1）水平及主動脈Wnt5a、β-catenin、p-GSK-3β蛋白表達(dá)水平明顯升高（P＜0.05），血清中高密度脂蛋白膽固醇（high-density lipoprotein cholesterol，HDL-C）、一氧化氮（nitric oxide，NO）水平及主動脈GSK-3β蛋白表達(dá)水平明顯降低（P＜0.05）；與模型組比較，黃芩苷低、中、高劑量組大鼠AS斑塊面積、血清LDL-C、TG、TC、TNF-α、IL-6、IL-1β、ET-1、ICAM-1水平及主動脈Wnt5a、β-catenin、p-GSK3β蛋白表達(dá)水平明顯降低（P＜0.05），血清中HDL-C、NO水平及主動脈GSK-3β蛋白表達(dá)水平明顯升高（P＜0.05），且呈劑量相關(guān)性；SKL2001顯著逆轉(zhuǎn)黃芩苷對AS大鼠的作用（P＜0.05）。結(jié)論 黃芩苷可能通過抑制Wnt/β-catenin信號通路抑制AS大鼠模型炎癥反應(yīng)。

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

江西省衛(wèi)生健康委科技計劃項目（202130277）