二甲双胍对牙周致病菌内毒素所致饮食诱导肥胖小鼠高血糖的改善作用  

Improvment effect of metformin on ameliorates hyperglycemia induced by lipopolysaccharide in diet induced obese mice

作　　者：王敏华 邓淑丽[2] 刘云西 陈菲菲 吴昊姝[1] WANG Min-hua;DENG Shu-li;LIU Yun-xi;CHEN Fei-fei;WU Hao-shu(Department of Pharmacology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China;Department of Conservative Dentistry, Affiliated Hospital of Stomatology , School of Medicine, Zhejiang University Hangzhou MOO06, China, Hangzhou MOO06, China;Department of Pharmacy, Affiliated Women＇s Hospital, School of Medicine, Zhefiang University, Hangzhou 310006, China)

机构地区：[1]浙江大学药学院药理学,杭州310058 [2]浙江大学医学院附属口腔医院牙髓科,杭州310006 [3]浙江大学医学院附属妇产科医院药剂科,杭州310006

出　　处：《中国临床药理学杂志》2018年第8期945-948,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81202969); 浙江省自然科学基金资助项目(LY17H140004); 浙江省中医药管理局一般研究计划基金资助项目(2016ZA134); 浙江省医药卫生一般研究计划基金资助项目(2016KYA118,2015KYB229)

摘　　要：目的观察牙周致病菌内毒素(PG LPS)对高脂饮食诱导肥胖(DIO)小鼠血糖的影响以及二甲双胍对糖尿病模型小鼠血糖的的对抗作用。方法按照体重将C57小鼠随机分为8组,每组6~8只:除正常组外,其余小鼠以高脂饲料喂养16周(共3组)或21周(共3组)建模;除高脂对照组外,糖尿病模型组每天腹腔注射PG LPS 100μg·kg^(-1);在上述处理的同时,二甲双胍组每天灌胃二甲双胍100 mg·kg^(-1),连续3周。用快速血糖仪测定血糖,以酶联免疫吸附法检测血浆胰岛素和肿瘤坏死因子-α(TNF-α)水平,用蛋白印迹法检测肝腺苷酸活化蛋白激酶(AMPK)信号通路蛋白的表达水平。结果给药后,21周高脂对照组、糖尿病模型组、二甲双胍组小鼠的血糖水平分别为(6.46±0.31),(7.82±0.35),(6.23±0.21)mmol·L^(-1),糖尿病模型组与高脂对照组比较,差异均有统计学意义(均P<0.05);二甲双胍组与糖尿病模型组比较,差异均有统计学意义(均P<0.01);糖尿病模型组、二甲双胍组小鼠的磷酸化AMPK(p-AMPK)的灰度值分别为1.03±0.04,1.62±0.21,组间比较差异有统计学意义(P<0.05)。结论二甲双胍是患牙周炎的肥胖高血糖患者的优选治疗药物。Objective To observe the impact of porphyromonas gingivalis（ PG） lipopolysaccharide（ LPS） on blood glucose of high-fat（ HF）diet-induced obese（ DIO） mice and the antagonistic effect of metformin on diabetes model mice. Methods The C57 mice were divided into 8 groups（ n = 6-8 in each group）. Apart from the normal control,mice were fed with HF diet for 16 weeks（ including 3 groups） or 21 weeks（ including 3 groups） for modeling. Besides the HF control group,the mice of diabetes model group and metformin group were given PG LPS 100μg·kg-（-1） with intraperitoneal injection and simultaneously administrated with 100 mg ·kg-1 metformin by gavage daily for 3 weeks,respectively. Blood glucose was measured with rapid glucometer. The plasma insulin and tumor necrosis factor-α（ TNF-α） were tested by enzyme linked immunosorbent assay. The expression of AMP-activated protein kinase（ AMPK） pathway protein in livers were detected by Western blotting.Results In 21 weeks DIO mice,the blood glucose levels in the HF control group,diabetes model group and metformin group were（ 6. 46 ± 0. 31）,（ 7. 82 ±0. 35）,（ 6. 23 ± 0. 21） mmol · L-（-1）, respectively. Comparisonbetween HF control group and diabetes model group,the difference was significant（ P〈0. 05）; comparison between diabetes model group and metformin group,the difference was significant（ P〈0. 01）. Expression of AMPK-phosphorylation status（ p-AMPK） in the diabetes model group and metformin group were 1. 03 ± 0. 04,1. 62 ± 0. 21,respectively. Comparison between diabetes model group and metformin group,the difference was significant（ P〈0. 05）.Conclusion Metformin is a preferred therapeutic agent for hyperglycemic patients with obesity and periodontitis.

关 键 词：内毒素 二甲双胍 高血糖 肥胖 牙龈卟啉单胞菌 

分 类 号：R977.15[医药卫生—药品]