金芪降糖片对糖尿病引发的认知功能障碍的影响及机制  

Effect and Mechanisms of Jinqi Jiangtang Tablet on Cognitive Dysfunction Induced by Diabetes

作　　者：杨丽[1] 徐利满 朱晓丹[2] 刘红玥 靳学海 宋丽丽[1] Alemu Paulos N 庄朋伟[1] 张艳军[1] 

机构地区：[1]天津中医药大学天津市中药药理重点实验室,天津300193 [2]天津中新药业集团股份有限公司隆顺榕制药厂,天津300457

出　　处：《中国实验方剂学杂志》2017年第1期146-152,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81403213);"十二五"期间天津市高等学校"创新团队培养计划"项目(TD12-5035)

摘　　要：目的:探讨金芪降糖片对糖尿病引发的认知功能障碍的影响,并初步探讨其作用机制。方法:选用C57BL/6J小鼠,采用ip链脲佐菌素(STZ,120 mg·kg-1)复合高脂饮食的方法诱导复制2型糖尿病模型。利用Morris水迷宫试验筛选出存在糖尿病认知功能障碍的小鼠,并随机将其分为4组,每组14只,分别为模型组,阳性药组(盐酸二甲双胍0.45 g·kg-1),金芪降糖片高(2倍临床等效剂量1.31 g·kg-1)及低(临床等效剂量0.655 g·kg-1)剂量组。正常组和模型组均给予等量蒸馏水,连续ig给药10周。在给药前及给药10周后,各测一次小鼠的空腹血糖(FBG)和体重。10周后,Morris水迷宫实验检测小鼠学习忆能力;尼式染色观察海马CA1区形态学变化;酶联免疫吸附测定(ELISA)检测小鼠血清脑源性神经营养因子(BDNF)水平;实时荧光定量聚合酶链式反应(Real-time PCR)法检测小鼠海马组织突触素(SYN)mRNA表达水平。结果:与正常组比较,模型组糖尿病小鼠FBG明显升高,记忆能力下降,海马神经损伤明显,血清BDNF水平明显降低,海马SYN mRNA表达水平明显降低,体重明显降低(P<0.05,P<0.01);与模型组比较,金芪降糖片高剂量组可降低糖尿病小鼠FBG,改善学习记忆能力,改善海马神经损伤状况,显著升高血清BDNF水平,显著增加海马SYN mRNA表达水平,各治疗组小鼠体重较稳定,差异均具有统计学意义(P<0.05,P<0.01)。结论:金芪降糖片可以改善糖尿病小鼠的学习记忆能力,可能是通过上调BDNF含量对海马神经细胞保护及营养修复,并促进海马SYN mRNA表达上调调节海马神经突触可塑性实现的。Objective： To explore the effects and initial mechanisms of Jinqi Jiangtang tablet on the cognitive dysfunction induced by diabetes. Method： C57 BL /6J mice received STZ（120 mg·kg^-1） by single intraperitoneal injection combined with high fat food to induce type 2 diabetic mice models. After 8 weeks,Morris water maze test was carried out to select the mice with cognitive dysfunction,then the selected ones were randomly divided into model group,metformin hydrochloride positive drug group,high dose（twice the clinical equivalent dose,1. 31 g·kg^-1） and low dose（clinical equivalent dose,0. 655 g·kg^-1） Jinqi Jiangtang tablet groups,n = 14 in each group. The mice in normal group and model group received the same volume of distilled water for 10 weeks. Fasting blood glucose（FBG） and body weight of the mice were measured once respectively before and after administration for 10 weeks. After treatment for 10 weeks,the learning and memory ability was tested by Morris water maze; morphological changes of the hippocampus CA1 area were observed by Nissl staining; the levels of brain derived neurotrophic factor（BDNF） in serum were detected by ELISA; synaptophysin（SYN） mRNA expression level in hippocampus was tested by Real-time PCR. Result： As compared with the normal group,FBG level was significantly increased in mice of model group; memory ability was reduced; with obvious hippocampal nerve injury,and serum BDNF levels were significantly decreased; SYN mRNA expression level in hippocampus was significantly reduced,and the body weight was also reduced（P〈0. 05,P〈0. 01）. As compared with the model group,Jinqi Jiangtang tablet high dose group could decrease the level of fasting blood-glucose of the diabetic mice,improve the learning and memory ability and hippocampal nerve injury,significantly increase the level of the serum BDNF and SYN mRNA expression in hippocampus; the body weight in mice of various treatment groups was stable,with statistical difference（P〈0. 05,P〈0. 01）. Conc

关 键 词：糖尿病 认知障碍 金芪降糖片 突触素 脑源性神经营养因子 

分 类 号：R285.5[医药卫生—中药学]