目的 通过核因子-κB（NF-κB）信号通路探讨鞣花酸对代谢相关性脂肪性肝病的效果及作用机制。方法 将SD大鼠按随机数字法分为对照组、模型组、水飞蓟宾组、鞣花酸（20、40、80 mg/kg）组，每组12只。采用高脂饲料喂养12周建立代谢相关性脂肪性肝病模型。收集大鼠肝组织及血清，采用HE和油红O染色观察肝脏病理变化，检测血清肝功能[天冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）]、血脂指标[高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、甘油三酯（TG）、总胆固醇（TC）]及炎症因子[白细胞介素（IL）-1α、IL-6、肿瘤坏死因子（TNF-α）]水平，并采用Western blotting检测肝组织中核因子-κB（NF-κB）p65、p-NF-κB p65、核因子κB抑制蛋白α（IkB-α）、IκB激酶β（IKK-β）、p-IKK-β蛋白的表达。结果 肝组织HE及油红O染色结果显示，与模型组相比，水飞蓟宾组及鞣花酸组均能明显减轻脂质沉积，肝细胞形态结构得到改善。与模型组比较，鞣花酸组ALT、AST、TC、TG、LDL-C、IL-1α、IL-6、TNF-α水平均显著降低，HDL-C显著升高（P＜0.05）。Western blotting结果显示，与模型组比较，鞣花酸组肝组织中p-NF-κB p65/NF-κB p65、p-IKK-β/IKK-β比值显著降低，而IκB-α表达显著上升（P＜0.05）。结论 鞣花酸能够有效改善高脂高糖饮食诱导的代谢相关性脂肪性肝病大鼠肝脏脂质沉积、肝功能损伤及炎症反应，其机制可能与调控经典NF-κB信号通路有关。

Objective To explore the effect and mechanism of ellagic acid on metabolism-related fatty liver disease through NF-κB signaling pathway. Methods SD rats were randomly divided into the control group, the model group, the silybin group, and the ellagic acid (20, 40, 80 mg/kg) groups according to the random number method, with 12 rats in each group. A metabolism-related fatty liver disease model was established by feeding with high-fat diet for 12 weeks. Liver tissues and sera of rats were collected, and the pathological changes of the liver were observed by HE and oil red O staining. Serum liver function (AST, ALT), lipid indicators (HDL-C, LDL-C, TG, TC), and inflammatory factors (IL-1α, IL-6, TNF-α) were detected. And the expressions of NF-κB p65, p-NF-κB p65, IkB-α, IKK-β, and p-IKK-β proteins in liver tissues were detected by Western blotting. Results The results of HE and oil red O staining of liver tissue showed that compared with the model group, both the silybin group and the ellagic acid group could significantly reduce lipid deposition, and the morphological structure of liver cells was improved. Compared with the model group, the levels of ALT, AST, TC, TG, LDL-C, IL-1α, IL-6, and TNF-α in the ellagic acid group were significantly decreased, and HDL-C was significantly increased (P < 0.05). The results of Western blotting showed that compared with the model group, the ratios of p-NF-κB p65/NF-κB p65, and p-IKK-β/IKK-β in liver tissues of the ellagic acid group were significantly decreased, while the expression of IκB-α was significantly increased (P < 0.05). Conclusion Ellagic acid can effectively improve hepatic lipid deposition, liver function impairment, and inflammatory responses in metabolism-related fatty liver disease rats induced by a high-fat/high-sugar diet, and its mechanism may be closely related to the inhibition of abnormal activation of the classical NF-κB signaling pathway and the reduction of pro-inflammatory cytokine expression.

R286.5

云南省重点实验室项目（YPKLS2024-005）