摘　要：基于Nrf2/HO-1/NLRP3通路探究雪莲果提取物治疗四氯化碳（CCl4）致急性肝损伤（ALI）大鼠的保护作用及机制。选取48只健康雄性SD大鼠，随机分为6组，分别为对照组、模型组、雪莲果低中高剂量组和水飞蓟素阳性组。利用CCl4构建急性肝损伤模型后处死大鼠取材，检测大鼠血清和肝脏生化指标，利用HE染色观察各组肝脏组织病理学改变情况；利用ELISA检测大鼠血清中炎症因子IL-6、TNF-α、IL-1β的表达水平；采用蛋白免疫印迹法测定大鼠肝组织中Nrf2/HO-1/NLRP3通路关键基因蛋白含量表达情况。结果表明：与正常对照组比较，模型组大鼠血清中AST、ALT、ALP、γ-GT、MDA、IL-6和TNF-α的表达水平均显著升高（P<0.05或P<0.01）；肝脏组织中SOD和GSH的表达水平均显著降低（P<0.05），大鼠肝组织细胞出现明显的病理性损伤（P<0.05）；与模型组比较，雪莲果提取物能够呈剂量依赖性降低大鼠血清中AST、ALT、ALP、γ-GT、IL-6和TNF-α的表达水平（P<0.05或P<0.01），以及提高肝脏组织中SOD、CAT、GSH和降低MDA的表达水平（P<0.05），大鼠肝组织病变程度明显改善，肝脏内细胞坏死和肿胀程度明显减轻，炎症细胞浸润得到显著改善。水飞蓟素阳性组能够显著改善大鼠肝损伤（P<0.05或P<0.01）。雪莲果提取物组与模型组比较，Nrf2、GCLC、NQO1和HO-1蛋白表达水平呈剂量依赖性升高（P<0.05或P<0.01）；NLRP3炎症小体相关蛋白（NLRP3、Caspase1、GSDMD和IL-18）表达水平呈剂量依赖性降低（P<0.05或P<0.01）。雪莲果提取物对CCl4所致的大鼠急性肝损伤具有保护作用，该作用可能与调节Nrf2/HO-1通路改善氧化应激，降低脂质过氧化，清除大鼠体内自由基，抑制NLRP3炎症小体的功能，减少炎症因子的合成与释放以及降低炎症反应有关。
关键词：雪莲果提取物；急性肝损伤；Nrf2/HO-1通路；NLRP3炎症小体；氧化应激
中图分类号：R287　　　　　       文献标志码：A               DOI：10.3969/j.issn.1007-7146.2023.03.010

Abstract: Based on Nrf2/HO-1/NLRP3 pathway, the protective effects and mechanism of yacon extract on acute liver injury (ALI) induced by carbon tetrachloride (CCl4) in rats were investigated. Forty-eight healthy male SD rats were randomly divided into 6 groups: control group, model group, low, medium and high dose group and silymarin positive group, in which ALI model was established with CCl4 and the rats were sacrificed for sampling, and the serum and liver biochemical indexes of rats were detected. HE staining was used to observe the histopathological changes of liver in each group, and ELISA was used to detect the expression levels of inflammatory cytokines IL-6, TNF-α and IL-1β in serum of rats. The relative expression of Nrf2/HO-1/NLRP3 pathway related proteins in rat liver was determined by Western blot. The results showed that compared with normal control group, the expression levels of AST, ALT, ALP, γ-GT, MDA, IL-6 and TNF-α in serum of rats in model group significantly increased (P<0.05 or P<0.01), while the expression levels of SOD, CAT, and GSH in liver tissue were significantly decreased (P<0.05). The pathological injury of rat liver tissue cells was obvious (P<0.05 or P<0.01). Compared with model group, the extract of yacon could decrease the expression levels of AST, ALT, ALP, γ-GT, IL-6 and TNF-α in serum in a dose-dependent manner (P<0.05 or P<0.01), which increase the expression levels of SOD, CAT and GSH and decrease the expression levels of MDA in liver tissue (P<0.05). The degree of liver tissue lesions in rats was significantly improved, which the degree of liver cell necrosis and swelling was significantly reduced, and the inflammatory cell infiltration was significantly improved. Silymarin positive group significantly improved rat liver injury (P<0.05 or P<0.01). Compared with model group, the protein expression levels of Nrf2, GCLC, NQO1 and HO-1 in the extract group and positive control group dose-dependenty increased (P<0.05 or P<0.01). The expression levels of NLRP3 inflammator-related proteins (NLRP3, Caspase1, GSDMD and IL-18) were reduced in a dose-dependent manner (P<0.05 or P<0.01). Yacon extracts have a protective effect on acute liver injury in rats caused by CCl4, in which the effect may be related to regulating Nrf2/HO-1 pathway to improve oxidative stress, reducing lipid peroxidation, removing free radicals in mice, inhibiting inflammatory corpuscle NLRP3 function, reducing the synthesis and release of inflammatory factors and reducing inflammation.
Key words: yacon extract; acute liver injury; Nrf2/HO-1 pathway; NLRP3 inflammasome; oxidative stress
（Acta Laser Biology Sinica, 2023, 32(3): 272-281）