竹节参总皂苷通过调节FGF21抵抗改善高脂饮食诱导的焦虑症  

Saponins from Panax japonicus ameliorate high-fat diet-induced anxiety by modulating FGF21 resistance

作　　者：黄艳 岳博文 胡月琴[2] 李维丽 余典梅 许杰 王金娥 周志勇[1,4] HUANG Yan;YUE Bo-wen;HU Yue-qin;LI Wei-li;YU Dian-mei;XU Jie;WANG Jin-e;ZHOU Zhi-yong(Third-grade Pharmacological Laboratory on Traditional Chinese Medicine Approved by State Administration of Traditional Chinese Medicine,College of Health Sciences,China Three Gorges University,Yichang 443002,China;the First College of Clinical Medical Science,China Three Gorges University,Yichang 443000,China;Basic Medical College,China Three Gorges University,Yichang 443002,China;Hubei Clinical Research Center for Functional Digestive Diseases of Traditional Chinese Medicine,Yichang 443199,China)

机构地区：[1]三峡大学健康医学院国家中医药管理局中药药理三级实验室,湖北宜昌443002 [2]三峡大学第一临床医学院,湖北宜昌443000 [3]三峡大学基础医学院,湖北宜昌443002 [4]湖北省功能性消化系统疾病中医临床医学研究中心,湖北宜昌443199

出　　处：《中国中药杂志》2025年第1期29-41,共13页China Journal of Chinese Materia Medica

基　　金：宜昌市医疗卫生研究项目(A22-2-023,A23-1-075);湖北省功能性消化系统疾病中医临床医学研究中心开放基金项目(SXZ202307);宜昌市公立医院改革与高质量发展示范项目中医药科技研发专项(YWGZ24-15)。

摘　　要：焦虑症是高发的心理疾病,研究表明肥胖是导致焦虑症的重要危险因素。该研究探讨竹节参总皂苷(saponins from Panax japonicus,SPJ)对高脂饮食小鼠焦虑症的改善作用及机制。将50只C57BL/6J小鼠随机分为正常组、高脂饮食组、SPJ低剂量组、SPJ高剂量组。第12周从高脂饮食组取6只小鼠,分为对照组、外源性给予成纤维细胞生长因子21(FGF21)组。旷场和高架十字迷宫实验评价小鼠焦虑样行为;苏木素-伊红(HE)染色和油红O染色观察肝脏、脂肪的病理变化;葡萄糖耐量实验和胰岛素耐量实验评估小鼠糖代谢水平;蛋白免疫印迹法检测肝脏和皮层中FGF21及下游相关蛋白和大脑皮层中脑源性神经营养因子(BDNF)、突触后膜蛋白4(DLG4)和突触素(SYP)表达;实时荧光定量PCR(qPCR)检测肝脏和皮层中FGF21及相关受体基因表达;免疫荧光检测大脑皮层神经元激活物(c-Fos)、FGF21、FGF21辅助受体β-klotho的表达。结果显示,SPJ可显著改善高脂饮食小鼠在高架十字迷宫的开臂区及旷场中心区的活动频率,并上调BDNF、DLG4和SYP表达,有效改善高脂饮食小鼠的焦虑样行为。与正常组相比,高脂饮食组小鼠的肝脏及大脑皮层中FGF21的表达上调,成纤维细胞生长因子受体1(FGFR1)与β-klotho的表达显著下降,提示高脂饮食小鼠呈FGF21抵抗状态;SPJ可显著上调高脂饮食小鼠β-klotho水平,逆转FGF21抵抗。进一步与外源性给予FGF21进行对比,显示SPJ激活大脑皮层区域与其一致,同时SPJ能促进大脑皮层中c-Fos与β-klotho阳性细胞数量及共定位。综上所述,SPJ可有效改善高脂饮食小鼠的焦虑样行为,其机制与上调大脑β-klotho表达,逆转FGF21抵抗,进而激活大脑皮层、杏仁核神经元有关。Anxiety disorder is a highly prevalent psychological illness,and research has shown that obesity is a significant risk factor for its development.This study explored the ameliorative effects and mechanisms of saponins from Panax japonicus(SPJ)on anxiety disorder in mice fed a high-fat diet(HFD).Fifty C57BL/6J mice were randomly divided into normal control diet(NCD)group,HFD group,and low-and high-dose SPJ groups.At week 12,six mice from the HFD group were further divided into a control group(treated with DMSO)and an exogenous fibroblast growth factor 21(FGF21)group(administered rFGF21).The anxiety-like behavior of the mice was assessed using the open field test and elevated plus maze test.Hematoxylin-eosin(HE)staining and oil red O staining were performed to observe pathological changes in the liver and adipose tissue.Glucose metabolism was evaluated through the glucose tolerance test(GTT)and insulin tolerance test(ITT).Western blot analysis was performed to detect the expression of FGF21 and its downstream-related proteins in the liver and cortex,along with the expression of brain-derived neurotrophic factor(BDNF),disks large homolog 4(DLG4),and synaptophysin(SYP)in the cortex.Real-time quantitative fluorescent PCR(qPCR)was used to detect the expression of FGF21 and its receptor genes in the liver and cortex.Immunofluorescence staining was employed to examine the expression of neuronal activator c-Fos,FGF21,and the FGF21 co-receptorβ-klotho in the cerebral cortex.The results showed that SPJ significantly improved the frequency of activity in the open arms of the elevated plus maze and the central area of the open field in HFD mice,up-regulated the expression of BDNF,DLG4,and SYP,and effectively alleviated anxiety-like behaviors in HFD mice.Compared with the NCD group,HFD mice exhibited up-regulated expression of FGF21 in the liver and cerebral cortex,while the expression of fibroblast growth factor receptor 1(FGFR1)andβ-klotho was significantly down-regulated,suggesting that HFD mice exhibited FGF21 resistance

关 键 词：竹节参总皂苷 焦虑症 高脂饮食 FGF21抵抗 FGF21-FGFR1/β-klotho信号通路 

分 类 号：R285.5[医药卫生—中药学]