人参皂苷Rb1改善拘束应激合并脂多糖诱导的小鼠免疫性肝损伤的作用机制研究  

Mechanism of ginsenoside Rb1 on improving restraint stress and lipopolysaccharide-induced immune liver injury in mice

作　　者：王国恩 杨帆[1] 刘心雨 叶钰菁 王若鸿 吕茜婷 刘小婷 WANG Guo-en;YANG Fan;LIU Xin-yu;YE Yu-jing;WANG Ruo-hong;LYU Xi-ting;LIU Xiao-ting(Guangdong Pharmaceutical University,Guangzhou 510006,China)

机构地区：[1]广东药科大学,广东广州510006

出　　处：《中草药》2022年第13期4028-4034,共7页Chinese Traditional and Herbal Drugs

基　　金：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)。

摘　　要：目的研究人参皂苷Rb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Rb(15 mg/kg)共7 d,给予RS(18 h)合并15μg/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Rb的潜在信号通路并加以验证。结果人参皂苷Rb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Rb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Rb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Rb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 Rbon immune liver injury induced by restraint stress(RS)combined with lipopolysaccharide(LPS)in mice.Methods BALB/c mice were pre-administered with ginsenoside Rb(15 mg/kg)for 7 d,mice were given RS(18 h)combined with 15μg/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 Rbwas predicted and verified by network pharmacology.Results Ginsenoside Rbameliorated 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 Rbhad 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 Rbwas 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 Rbhas 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.

关 键 词：人参皂苷RB1 免疫性肝损伤 氧化应激 Sirtuin-3 超氧化物歧化酶 

分 类 号：R285.5[医药卫生—中药学]