番石榴叶提取物对db/db小鼠骨骼肌AMPK-PGC-1α-FNDC5信号通路的影响  

Effects of guava leaf extracts on AMPK-PGC-1α-FNDC5 signaling pathway in skeletal muscle of db/db mice

作　　者：梁凡 苏通 刘铜华[4] 高明 盛彤[3] 王颖[3] 郭翔宇[3] LIANG Fan;SU Tong;LIU Tonghua(Fuxing Hospital of Beijing City,Capital Medical University,Beijing 100038)

机构地区：[1]首都医科大学附属复兴医院,北京100038 [2]北京市西城区月坛社区卫生服务中心,北京100038 [3]北京中医药大学东方医院,北京100078 [4]北京中医药大学,北京100029 [5]日本武库川女子大学药学部,日本兵库6638179

出　　处：《陕西中医》2020年第7期849-852,共4页Shaanxi Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金资助项目(81303130);北京中医药大学杰出青年人才项目(BUCM-2019-JCRC009);北京中医药大学东方医院1166人才培养项目(040204001001002022)。

摘　　要：目的:探讨番石榴叶提取物对糖尿病db/db小鼠骨骼肌AMPK-PGC-1α-FNDC5信号通路的影响。方法:实验共纳入24只6周龄雄性db/db小鼠及6只同龄雄性C57BL/6J小鼠,适应性喂养两周后,6只C57BL/6J雄性小鼠作为正常组,db/db小鼠检测空腹血糖≥7.0 mmol/l者视为造模成功,并随机分为模型组和番石榴叶提取物高、中、低剂量组,每组各6只。番石榴叶提取物按高剂量14 mg/kg、中剂量7 mg/kg、低剂量3.5 mg/kg每日进行灌胃,正常组小鼠灌服等量蒸馏水,干预4周。每周监测小鼠进食量、体重和空腹血糖。实验结束后,将小鼠空腹脱臼处死,并从眼眶取血,测定血浆胰岛素水平。Western-blot检测AMPK-α、p-AMPK-α、PGC-1α、FNDC5蛋白在骨骼肌中的表达,以及PGC-1α、UCP-1在脂肪组织中的表达。结果:番石榴叶提取物高剂量组小鼠相比模型组小鼠体重、血糖均显著降低,中剂量组小鼠在第2周血糖也出现明显下降,高、中剂量组小鼠的胰岛素水平均降低。检测蛋白表达结果显示,番石榴叶提取物干预的小鼠骨骼肌P-AMPK-α、PGC-1α、FNDC5蛋白和脂肪组织PGC-1α、UCP-1蛋白的表达均明显高于模型组。结论:番石榴叶提取物可通过增强骨骼肌的AMPK-PGC-1α-FNDC5信号通路传导,诱导白色脂肪组织棕色化,以实现降低血糖、减轻体重。Objective:To observe the effects of Guava leaf extracts on AMPK-PGC-1α-FNDC5 signaling pathway in db/db mice skeletal muscle.Methods:A total of 246-weeks-old male db/db mice and 6 male C57BL/6J mice of the same age were included in the experiment.After two weeks of adaptive feeding,6 C57BL/6J male mice were used as the normal group.db/db mice with fasting blood glucose≥7.0 mmol/l were considered as successful in modeling,and randomly divided into model group and Guava leaf extract high,medium and low dose groups,6 in each group.The guava leaf extracts were intragastrically administered at a high dose of 14 mg/kg,a medium dose of 7 mg/kg,and a low dose of 3.5 mg/kg,and mice in the normal group were given the same amount of distilled water for 4 weeks.The food intake,body weight and fasting blood glucose of the mice were monitored weekly.After the experiment,the mice were sacrificed by fasting dislocation,and blood was taken from the orbit to determine the plasma insulin level.Western-blot detected the expression of AMPK-α,p-AMPK-α,PGC-1α,FNDC5 protein in skeletal muscle,and the expression of PGC-1α,UCP-1 in adipose tissue.Results:Body weight and fasting blood glucose levels of high-dose Guava leaf extracts group were reduced,and fasting blood glucose level of medium-dose group also reduced in second week.P-AMPK-α、PGC-1α、FNDC5 protein expression of skeletal muscle and PGC-1α、UCP-1 protein expression of adipose tissue were decreased in Guava leaf extracts groups.Conclusion:Guava leaf extracts can induce the browning of white tissues by enhancing the AMPK-PGC-1α-FNDC5 signal transmission pathway of skeletal muscle,so as to reduce blood sugar and body weight.

关 键 词：番石榴叶 DB/DB小鼠 骨骼肌 棕色脂肪 腺苷酸活化蛋白激酶 

分 类 号：R587.1[医药卫生—内分泌]