摘 要：为探究牛蒡子苷元（ATG）通过激活核因子E2相关因子2（Nrf2）/血红素加氧酶1（HO-1）信号通路和抑制NF-κB信号通路对庆大霉素（GM）所致急性肾损伤（AKI）大鼠的治疗作用和机制，本研究选取36只雄性SD大鼠，随机分为对照组（6只）和造模组（30只）。造模组连续7 d腹腔注射100 mg/kg GM建立AKI模型，造模成功的大鼠随机分为模型组、阳性对照组（5 mg/kg盐酸贝那普利）和ATG低、中、高（1、3、9 mg/kg ATG）剂量组，每组6只。检测大鼠血清尿素氮（BUN）、肌酐（SCR）、肾组织超氧化物歧化酶（SOD）、还原型谷胱甘肽（GSH）、过氧化氢酶（CAT）、丙二醛（MDA）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、肾损伤分子-1（KIM-1）的水平以及Nrf2、HO-1、核因子κB p65（NF-κB p65）的mRNA和蛋白表达水平。与模型组相比，ATG治疗后，大鼠血清BUN和SCR水平显著降低（P<0.01）。在肾组织中，抗氧化指标（SOD、CAT、GSH）以及Nrf2/HO-1通路关键因子（Nrf2、HO-1）的mRNA和蛋白表达均显著上调（P<0.05或P<0.01）；而氧化损伤产物（MDA）、炎症因子（IL-1β、IL-6、TNF-α）、肾损伤标志物（KIM-1）以及NF-κB p65的mRNA和蛋白表达均显著下调（P<0.05或P<0.01）。组织病理学检查显示，ATG治疗组大鼠的肾小管上皮细胞形态改善，萎缩、纤维化和炎性浸润减轻。本研究结果表明，ATG通过协同激活Nrf2/HO-1通路以增强抗氧化能力，并抑制NF-κB通路以减轻炎症反应，从而对GM所致AKI发挥多靶点治疗作用，为其临床转化提供了理论依据。

关键词：牛蒡子苷元；庆大霉素；急性肾损伤；核因子E2相关因子2/血红素加氧酶1信号通路；核因子κB信号通路
中国分类号：R285.5                   文献标志码：A                 DOI：10.3969/j.issn.1007-7146.2025.05.007

Abstract: To investigate the therapeutic effect and mechanism of arctigenin (ATG) on gentamicin (GM) induced acute kidney injury (AKI) in rats via activating the nuclear factor erythroid 2-related factor 2(Nrf2) / heme oxygenase-1(HO-1) signaling pathway and inhibiting the NF-κB signaling pathway, 36 male SD rats were selected and randomly divided into a control group (6 rats) and a model establishment group (30 rats). The model group received intraperitoneal injection of 100 mg/kg GM for 7 consecutive days to establish the AKI model. The successfully modeled rats were then randomly assigned to the model group, positive control group (5 mg/kg benazepril hydrochloride), and ATG low-, medium-, and high-dose groups (1, 3, 9 mg/kg ATG), with 6 rats in each group. The following parameters were measured: serum urea nitrogen (BUN) and creatinine (SCR) levels; renal tissue levels of superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), malondialdehyde (MDA), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and kidney injury molecule-1(KIM-1), as well as the mRNA and protein expression levels of Nrf2, HO-1, and nuclear factor-kappa B p65 (NF-κB p65). Compared with the model group, ATG treatment significantly reduced serum levels of BUN and SCR in rats (P<0.01). In renal tissues, it markedly upregulated the mRNA and protein expression of antioxidant indicators (SOD, CAT, GSH) and key factors of the Nrf2/HO-1 pathway (Nrf2, HO-1) (P<0.05 or P<0.01), while downregulating the expression of oxidative damage product (MDA), inflammatory factors (IL-1β, IL-6, TNF-α), kidney injury marker (KIM-1), as well as NF-κB p65 mRNA and protein (P<0.05 or P<0.01). Histopathological examination revealed that ATG treatment improved renal tubular epithelial cell morphology, attenuated tubular atrophy, fibrosis, and inflammatory infiltration. These results demonstrate that ATG exerts a multi-target therapeutic effect on GM-induced AKI by synergistically activating the Nrf2/HO-1 pathway to enhance antioxidant capacity and inhibiting the NF-κB pathway to alleviate inflammatory response, thereby providing a theoretical basis for its clinical translation.
Key words: actigenin; gentamicin; acute kidney injury; nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling pathway; nuclear factor-kappa B signaling pathway
（Acta Laser Biology Sinica, 2025, 34(5): 442-450）