摘要
目的:观察人参皂苷Rb1对肥胖模型小鼠体质量、体成分、血脂、骨骼肌耐力及胰岛素敏感性等指标的影响,研究其药理作用;并进一步探讨其对骨骼肌AMPK信号通路的影响。方法:选取8周龄C57BL/6J小鼠高脂喂养12周诱导肥胖模型,将成模小鼠随机分为模型对照组,二甲双胍组,人参皂苷Rb1组,以正常饲料喂养的小鼠作为正常对照,给药干预8周。每周定期检测小鼠体质量、摄食量;第3和7周行小鼠跑台实验;第4和8周行口服葡萄糖耐量实验;第8周用磁共振成像清醒动物体成分分析仪检测小鼠体成分;实验结束后取材,检测血脂4项及游离脂肪酸水平,实时荧光定量PCR检测骨骼肌组织单磷酸腺苷活化蛋白激酶(AMPK)α及过氧化物酶体增殖物激活受体γ共激活因子1(PGC-1)α的mRNA水平,免疫印迹法检测脂肪组织AMPKα、p-AMPKα,PGC-1α蛋白的表达。结果:人参皂苷Rb1组小鼠体质量(自给药第5周起)、摄食量均明显低于模型对照组小鼠(P <0. 05),有一定的时效关系。人参皂苷Rb1可显著降低三酰甘油、低密度脂蛋白胆固醇,提高高密度脂蛋白胆固醇的水平,并降低血清游离脂肪酸水平(P <0. 05)。人参皂苷给药8周可降低肥胖小鼠体脂肪含量,并增加筋肌含量(P <0. 05),增加小鼠骨骼肌运动耐力(P <0. 05),改善其口服糖耐量。人参皂苷Rb1能上调肥胖小鼠骨骼肌组织AMPKαmRNA及蛋白表达,且p-AMPKα蛋白表达亦明显增加(P <0. 05),同时提高肥胖小鼠骨骼肌组织PGC-1α的mRNA及蛋白表达(P <0. 05)。结论:人参皂苷Rb1能通过激活骨骼肌AMPK信号通路相关蛋白,达到减轻肥胖小鼠体质量,降低血脂水平,提高骨骼肌耐力,并增加其胰岛素敏感性的作用。
Objective: To observe the effects of ginsenoside Rb1 on body weight,body composition,blood lipid,skeletal muscle endurance and insulin sensitivity in obese mice,and further explore its effects on AMPK signaling pathway in skeletal muscle. Methods: 8-week-old C57BL/6J mice were fed with high fat diet for 12 weeks to induce obese mice model.The obese mice were randomly divided into three groups(the model control group,the metformin group and the ginsenoside Rb1 group).The peer mice fed with normal diet was set as the normal control.The mice were administrated with corresponding drugs for 8 weeks.Body weight and food intake of the mice were measured regularly every week.Treadmill test was performed on the 3rd and 7th week,and the oral glucose tolerance test was conducted on the 4th and 8th week.Body composition of the mice was detected by NMR Animal Body Composition Analyzer on the 8th week.Four indexes of plasma lipids and free fatty acid levels were detected at the end of the study.The mRNA expressions of AMPKα and PGC-1α in skeletal muscle were examined by real-time fluorescence quantitative PCR(FQ-PCR),and the protein expression of AMPKα,p-AMPKα and PGC-1α were detected by Western blot. Results: The body weight(since the 5th week)and food intake of the mice in the ginsenoside Rb1 group were significantly lower than those in the model control group( P <0.05)in a relatively time-dependent manner.Ginsenoside Rb1 could significantly reduce the levels of triglyceride and low density lipoprotein cholesterol,while increase that of high density lipoprotein cholesterol( P <0.05).In addition,ginsenoside Rb1 reduced serum free fatty acid levels( P <0.05).After the administration of ginsenoside Rb1 for 8 weeks,the body fat mass of obese mice was decreased and the lean mass was increased,oppositely( P <0.05).The skeletal muscle endurance( P <0.05)and the oral glucose tolerance of the obese mice were improved by ginsenoside Rb1.At the molecular level,ginsenoside Rb1 could up-regulate the mRNA and protein expression of AMPKα in skeletal muscles,and the content of p-AMPK protein was also increased significantly( P <0.05).At the same time,the mRNA and protein expression level of PGC-1α were also up-regulated,correspondingly( P <0.01). Conclusion: Ginsenoside Rb1 exerts effects on reducing body weight,decreasing blood lipid levels,improving skeletal muscle endurance and insulin sensitivity in obese mice by activating AMPK signaling pathway in skeletal muscles.
作者
赵丹丹
白颖
吴瑞
莫芳芳
方心
田甜
马如风
柳辰玥
朱如愿
高思华
Zhao Dandan;Bai Ying;Wu Rui;Mo FangFang;Fang Xin;Tian Tian;Ma Rufeng;Liu Chenyue;Zhu Ruyuan;Gao Sihua(Traditional Chinese Medicine School,Beijing University of Chinese Medicine,Beijing 100029,China;Department of Endocrinology,South Area of Guang′anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 102618,China;Department of Endocrinology,Third Affiliated Hospital of Beijing University of Chinese Medicine,Beijing 100029,China)
出处
《世界中医药》
CAS
2019年第4期852-858,共7页
World Chinese Medicine
基金
国家自然科学基金项目(NSFC81503540&NSFC81274041)
朝阳区科委协同创新项目(CYXC1513)
重大新药创制子课题(2012ZX09103201-005)
北京市共建项目(0101216-14&0101216-2013)