早期二甲双胍治疗对糖尿病前期合并短暂局灶脑缺血后长期认知功能的影响

Effect of Early Metformin Treatment on Long-term Cognitive Function in Prediabetic Rats after Transient Focal Cerebral Ischemia

目的研究糖尿病前期对短暂局灶脑缺血后长期认知功能的影响,以及早期二甲双胍治疗的效果。方法给予6周龄的雄性Wistar大鼠高脂饮食构建糖尿病前期模型。糖尿病前期大鼠在10周龄时给予为期12周的二甲双胍治疗[200 mg/(kg·d),腹腔注射]。14周龄时进行90 min大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)术。分别在15、20周龄时进行Rotarod旋转棒实验评估运动功能。21周龄时进行Morris水迷宫实验评估认知功能。通过血糖检测试纸和ELISA的方法分别检测空腹血糖和血清胰岛素水平。结果糖尿病前期大鼠在MCAO术后其长期神经功能以及空间学习记忆能力较无糖尿病前期大鼠更差。早期二甲双胍治疗可改善糖尿病前期合并卒中后的认知功能障碍。二甲双胍治疗大鼠的空腹血糖和空腹胰岛素水平较生理盐水治疗更低。结论在糖尿病前期即启动二甲双胍治疗可减轻后期卒中导致的长期认知功能障碍,这可能与降低血糖和胰岛素水平有关。

Objective To investigate the influence of prediabetes on post-stroke cognitive function and the effect of metformin treatment at the stage of prediabetes on cognitive decline after stroke.Methods Six-week-old male Wistar rats were fed with high-fat diet to build prediabetes models. Prediabetes rats were given metformin treatment of 12 weeks [200 mg/（kg·d）, intraperitoneal injection] from an age of 10 weeks, and the rats were subjected to a 90-minute right middle cerebral artery occlusion（MCAO） at an age of 14 weeks. Rotarod tests were performed to evaluate motor coordination function in prediabetes rats at an age of 15 and 20 weeks, and then Morris water maze tests were conducted to evaluate these rats＇ cognitive function at an age of 21 weeks. The levels of fasting blood glucose and serum insulin were measured using blood glucose test strips and ELISA assay.Results Prediabetes rats had more worse long-term neurological function and ability of spatial learning and memory after MCAO than rats without prediabetes. Early metformin treatment could alleviate cognitive decline after stroke in prediabetes rats. The rats treated with metformin had lower concentration of blood glucose and serum insulin than rats treated with saline.Conclusions Early metformin treatment in the stage of prediabetes could alleviate long-term cognitive decline after stroke, which is probably associated with the lower level of blood glucose and insulin due to metformin.