丙戊酸钠对四氧嘧啶糖尿病小鼠的抗糖尿病作用研究  

Anti-diabetic effect of sodium valproate in alloxan-induced diabetic mice

作　　者：白国良 环奕 夏杰 王星 周甜 李荣翠 申竹芳 BAI Guo - liang;HUAN Yi;XIA Jie;WANG Xing;ZHOU Tian;LI Rong - cui;SHEN Zhu - fang(State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Key Laboratory of Polymorphic Drugs of Bering, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing IO00SO, Chin)

机构地区：[1]中国医学科学院北京协和医学院药物研究所天然药物活性物质与功能国家重点实验室晶型药物研究北京市重点实验室,北京100050

出　　处：《中国临床药理学杂志》2018年第13期1536-1538,1564,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金青年基金资助项目(81603027);中国医学科学院医学与健康创新工程基金资助项目(2017-I2M-1-010)

摘　　要：目的研究丙戊酸钠对四氧嘧啶糖尿病小鼠糖代谢和胰岛功能的影响。方法除正常组外,其余ICR小鼠尾静脉注射四氧嘧啶形成1型糖尿病模型,随机分为4组(n=10),分别为模型组、对照组和低、高2个剂量实验组。正常组和模型组小鼠灌胃给予蒸馏水,对照组灌胃二甲双胍水溶液150 mg·kg^(-1);低、高2个剂量实验组组分别灌胃给予200,400 mg·kg^(-1)丙戊酸钠。所有小鼠均每天灌胃1次,连续10周。试验期间定期记录小鼠体重和测定空腹血糖水平,于第8周和第9周分别进行口服葡萄糖耐量实验和测定糖化血红蛋白水平,实验结束后对小鼠胰腺进行免疫荧光分析,观察胰岛形态变化。结果低、高剂量实验组均可显著性降低四氧嘧啶糖尿病小鼠的空腹血糖,可分别降低糖化血红蛋白水平达13.8%和35.6%;改善口服糖耐量,使血糖曲线下面积降低18.1%和17.9%;胰岛面积分别增加208.5%和275.3%,胰岛β细胞数量分别增加392.8%和523.8%,改善糖尿病小鼠胰岛形态,并具有一定量效关系。结论丙戊酸钠对四氧嘧啶糖尿病小鼠具有抗糖尿病作用,其机制可能与胰岛功能改善有关。Objective To investigate the effect of sodium valproate（ VPA） on the glucose metabolism and islets function in alloxan-induced diabetic mice. Methods In addition to being the normal group,the other ICR mice were intravenously injected alloxan at dose of 85 mg·kg-1 to induce diabetic model and then divided randomly into four group（ n = 10） ： model group,control group and low,high dose experimental groups. The mice in normal group and model group were administrated with distilled water, control group was given 150 mg · kg-1 metformin,low and high dose experimental groups were given 200,400 mg·kg-1 VPA. All the mice were administrated by gavage once a day for 10 weeks. During the treatment, body weight and fasting blood glucose were monitored every other week. Oral glucose tolerance test and glycated hemoglobin（ Hb A1 c） levels were determined at 8 thand 9 th week,respectively. At the end of experiment,the pancreas section was carried out immunofluorescence analyses to explore the morphology of islets. Results Both low and high dose experimental groups can significantly reduce fasting blood glucose level and the Hb A1 c level by 13. 8%and 35. 6%; VPA could improve glucose tolerance,in fact,the areaunder the curve（ AUC） of oral glucose tolerance was decreased by 18. 1% and 17. 9%,respectively; VPA could expand the area of islets by 208. 5% and 275. 3%,respectively,increase the number of pancreas β cells by 392. 8%,523. 8%,respectively,and ameliorate the changes of islets morphology in alloxan-induced diabetic mice in a dose-dependent manner. Conclusion VPA possesses anti-diabetic effect in alloxan-induced diabetic mice,and the mechanism may be related to the improvement of islets function.

关 键 词：丙戊酸钠 1型糖尿病 组蛋白去乙酰化酶 

分 类 号：R977[医药卫生—药品]