环境与职业医学2024，Vol.41Issue(7)：751-759,9.DOI:10.11836/JEOM24072
基于网络药理学探讨银杏叶提取物改善砷暴露所致肝胰岛素抵抗的效果
Effect of Ginkgo biloba extract on improving hepatic insulin resistance induced by arsenic ex-posure based on network pharmacology
摘要
Abstract
[Background]Arsenic exposure is a common and important environmental and occupational hazardous factor in China,and arsenic-induced insulin resistance(IR)has attracted widespread attention as a negative health outcome to the population. [Objective]To explore part of the mechanism of hepatic IR induced by arsenic exposure based on the peroxisome proliferators-activated receptors γ(PPARγ)/glucose transporter 4(GLUT4)pathway,and to investigate potential effects of Ginkgo biloba extract(GBE)on hepatic IR induced by arsenic exposure and associated mechanism of action. [Methods]The target of drug action was predicted by network pharmacology and verified by in vivo and in vitro experiments.In vivo ex-periments:48 SPF C57BL/6J male mice were divided into 4 groups,including control group,50 mg·L-1 NaAsO2 model group(NaAsO2),50 mg·L-1 NaAsO2+10 mg·kg-1 GBE intervene group(NaAsO2+GBE),and 10 mg·kg-1 GBE group(GBE),12 mice in each group.The animals were given free access to purified water containing 50 mg·L-1 NaAsO2,or given intraperitoneal injection of normal saline containing 10 mg·kg-1 GBE once per week.After 6 months of exposure,blood glucose detection,intraperitoneal glucose tolerance test(IPGTT),and insulin tolerance test(ITT)were performed.Serum and liver tissues were collected after the mice were neutralized,liver histopathological sections were obtained,serum insulin levels,liver tissue glycogen content,glucose content were detected by enzyme linked immunosorbent assay(ELISA),and the expression of PPARγ and GLUT4 proteins was detected by Western blot(WB).In vitro experiments:HepG2 cells were divided into 4 groups,including control group,8 μmol·L-1 NaAsO2 group(NaAsO2),8 μmol·L-1 NaAsO2+200 mg·L-1 GBE intervene group(NaAsO2+GBE),and 200 mg·L-1 GBE group(GBE).The levels of glycogen and glucose were detected by ELISA,and the expression of PPARγ and GLUT4 proteins was detected by WB. [Results]A strong binding effect between GBE and PPARγ was revealed by network pharmacology.In in vivo experiments,the NaAsO2 group exhibited an elevated blood glucose compared to the control group,and the NaAsO2+GBE group showed a decreased blood glucose compared to the NaAsO2 group(P＜0.01).The histopathological sections indicated severe liver structural damage in the arsenic exposure groups(NaAsO2 group and NaAsO2+GBE group),with varying staining intensity,partial liver cell necrosis,and diffuse red blood cell ap-pearance.Both results of in vitro and in vivo experiments showed a decrease in glycogen synthesis and glucose uptake in the NaAsO2 groups compared to the control groups,which was alleviated in the NaAsO2+GBE group(P＜0.01).The results of WB revealed inhibited PPARγ expression and reduced GLUT4 levels on the cell membrane,and all these changes were alleviated in the NaAsO2+GBE group(P＜0.01). [Conclusion]This study findings suggest that GBE antagonizes arsenic exposure-induced hepatic IR by regulating the PPARγ/GLUT4 path-way,indicating that GBE has a protective effect on arsenic exposure-induced hepatic IR,and PPARγ may be a potential therapeutic target for arsenic exposure-induced hepatic IR.关键词
亚砷酸钠/肝胰岛素抵抗/二型糖尿病/银杏叶提取物/过氧化物酶体增殖物激活受体γ/葡萄糖转运蛋白4Key words
sodium arsenite/hepatic insulin resistance/type 2 diabetes mellitus/Ginkgo biloba extract/peroxisome proliferators-activated receptors γ/glucose transporter 4分类
医药卫生引用本文复制引用
胡志达,高艳荣,徐诗晴,孟茹茹,贾艳丰,张琪瑶,边博浩,王姝蕊,刘洋,王丽..基于网络药理学探讨银杏叶提取物改善砷暴露所致肝胰岛素抵抗的效果[J].环境与职业医学,2024,41(7):751-759,9.基金项目
国家自然科学基金项目(82060605) （82060605）
