目的 研究人参皂苷Rb₁对拘束应激（restraint stress，RS）合并脂多糖（lipopolysaccharide，LPS）诱导的免疫性肝损伤小鼠的保肝作用及其机制。方法 BALB/c小鼠预先给予人参皂苷Rb₁（15 mg/kg）共7 d，给予RS（18 h）合并15 μg/kg LPS诱发免疫性肝损伤。取小鼠肝脏进行组织学观察、免疫组化和生化指标检测，基因和蛋白表达检测，利用网络药理学预测人参皂苷Rb₁的潜在信号通路并加以验证。结果 人参皂苷Rb₁改善RS合并LPS诱导肝损伤小鼠的肝脏炎性细胞浸润、脂肪空泡以及炎症坏死现象；显著抑制肝组织白细胞介素-1β（interleukin-1β，IL-1β）、肿瘤坏死因子-α（tumor necrosis factor，TNF-α）、转化生长因子-β1（transforming growth factor-β1，TGF-β1）和超氧化物歧化酶（superoxide dismutase，SOD）表达（P＜0.05、0.01）；减少肝细胞凋亡；降低肝组织丙二醛（malondialdehyde，MDA）水平（P＜0.01）；升高肝组织SOD活性和去乙酰化酶Sirtuin-3（SIRT3）蛋白表达水平（P＜0.01）。人参皂苷Rb₁对LPS诱导的小鼠肝损伤及氧化应激影响不明显。结合网络药理学结果提示人参皂苷Rb₁改善氧化应激作用与上调SIRT3的下游靶标叉头框转录因子O3（forkhead box O3，FoxO3）的基因表达有关（P＜0.01）。结论 ：人参皂苷Rb₁对RS合并LPS诱导小鼠免疫性肝损伤有保护作用，其作用机制可能与上调SIRT3/FoxO3/SOD功能有关。

Objective To study the hepatoprotective effect and mechanism of ginsenoside Rb₁ on immune liver injury induced by restraint stress (RS) combined with lipopolysaccharide (LPS) in mice. Methods BALB/c mice were pre-administered with ginsenoside Rb₁ (15 mg/kg) for 7 d, mice were given RS (18 h) combined with 15 μg/kg LPS to induce immune liver injury. Liver was taken for histological observation, immunohistochemical and biochemical index detection, gene and protein expression detection, and potential signaling pathway of ginsenoside Rb₁ was predicted and verified by network pharmacology. Results Ginsenoside Rb₁ ameliorated hepatic inflammatory cell infiltration, fat vacuoles and inflammatory necrosis in RS combined with LPS-induced liver injury mice; Significantly inhibited interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1) and superoxide dismutase (SOD) expressions in liver tissue (P < 0.05, 0.01); Decreased hepatocyte apoptosis; Decreased malondialdehyde (MDA) level in liver tissue (P < 0.01); Increased SOD activity and sirtuin-3 (SIRT3) protein expression in liver tissue (P < 0.01). Ginsenoside Rb₁ had no obvious effect on LPS-induced liver injury and oxidative stress in mice. Combined with the results of network pharmacology, it was suggested that improvement of oxidative stress by ginsenoside Rb₁ was related to the up-regulation of gene expression of forkhead box O3 (FoxO3), which was the downstream target of SIRT3 (P < 0.01). Conclusion Ginsenoside Rb₁ has protective effect on immune liver injury induced by RS combined with LPS in mice, and its mechanism may be related to the up-regulation of SIRT3/FoxO3/SOD function.

R285.5

广东省基础与应用基础研究基金资助项目(2020A1515010894);广东省中医药管理局科研基金资助项目(20201195);广东省医学科研基金资助项目(B2019067,A2020615)