基于TLR4/MyD88/NF-κB信号通路研究人参皂苷Rb1对db/db肥胖小鼠肝脏脂肪变性的干预机制
Intervention mechanism of ginsenoside Rb1 on liver steatosis in db/db obese mice based on TLR4/MyD88/NF-κB signaling pathway
李婷婷 1张程斐 1郭翔宇1
作者信息
- 1. 北京中医药大学东方医院,北京 100078
- 折叠
摘要
基于 Toll 样受体 4(Toll-like receptor 4,TLR4)/髓样分化因子 88(myeloid differentiation factor 88,MyD88)/核因子 κB(nuclear factor kappaB,NF-κB)信号通路,观察人参皂苷Rb1(ginsenoside Rb1,Rb1)对db/db肥胖小鼠肝脏脂代谢的调节作用,并探究其潜在的作用机制.30只6周龄雄性db/db小鼠按体质量及空腹血糖随机分为模型组,二甲双胍组,Rb1低、中、高剂量组,每组6只.另设6只同周龄雄性db/m小鼠作为正常组,共干预5周.每周测量小鼠体质量、空腹血糖、摄食量,实验结束后,收集小鼠血清检测血脂及肝功能.苏木素-伊红染色、油红O染色观察肝脏组织病理变化.实时荧光定量PCR和免疫组织化学法分别检测TLR4、MyD88、NF-κB p65 mRNA和蛋白表达.结果显示,与正常组相比,模型组小鼠体质量、肝质量、肝脏指数、附睾脂肪质量、附睾脂肪指数、总胆固醇、低密度脂蛋白胆固醇、肝功能参数、空腹血糖显著升高;肝脏内脂肪蓄积显著增加;肝脏TLR4、MyD88、NF-κB p65 mRNA及蛋白表达显著增加.经Rb1处理后,干预组小鼠上述指标明显逆转.总之,Rb1可改善小鼠肥胖及肥胖相关性肝脏脂肪变性,同时具有调节血脂和糖代谢异常的作用,从机制分析Rb1可能通过调控TLR4/MyD88/NF-κB信号通路改善db/db肥胖小鼠肝脏脂肪变性.
Abstract
Based on the Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor kappaB(NF-κB)signaling pathway,this study observed the regulatory effect of ginsenoside Rb 1(Rb 1)on liver lipid metabolism in db/db obese mice and explored its potential mechanism.Thirty 6-week-old male db/db mice were randomly divided into a model group,a metformin group,and Rb1 groups with low,medium,and high doses,with six mice in each group.Additionally,six age-matched male db/m mice were assigned to the normal group.The intervention lasted for five weeks.Body weight,fasting blood glucose,and food intake were mea-sured weekly.At the end of the experiment,serum lipid levels and liver function were detected.Hematoxylin-eosin(HE)staining and oil red O staining were performed to observe pathological changes in liver tissue.Real-time quantitative PCR and immunohistochemistry on paraffin sections were used to detect the mRNA and protein expression of TLR4,MyD88,and NF-κB p65.Results showed that compared with the normal group,the model group exhibited significant increases in body weight,liver weight,liver index,epididymal fat mass,epididymal fat index,total cholesterol,low-density lipoprotein cholesterol,liver function parameters,and fasting blood glu-cose levels.Liver lipid accumulation significantly increased,along with elevated mRNA and protein expression of TLR4,MyD88,and NF-κB p65 in the liver.After Rb1 treatment,the above-mentioned parameters in the intervention groups showed significant reversals.In conclusion,Rb1 can improve obesity and obesity-related hepatic steatosis in mice while regulating abnormal lipid and glucose meta-bolism.Mechanistically,Rb1may improve liver steatosis in db/db obese mice by modulating the TLR4/MyD88/NF-κB signaling path-way.
关键词
人参皂苷Rb1/db/db小鼠/肝脏脂肪变性/TLR4/MyD88/NF-κB信号通路/肥胖Key words
ginsenoside Rb1/db/db mice/hepatic steatosis/TLR4/MyD88/NF-κB signaling pathway/obesity引用本文复制引用
基金项目
国家自然科学基金面上项目(82174351)
出版年
2024
NETL
NSTL
万方数据