摘要
目的:研究基于糖尿病认知功能障碍发病的核心病机:糖脂毒"毒损脑络",拟从中医辩证的角度建立稳定、可靠的糖尿病认知功能障碍小鼠模型,以期为中药及民族药防治糖尿病及其并发症研究提供科学的实验工具.方法:分别建立高糖模型、高糖高脂模型,以及不同剂量D-半乳糖+高糖高脂复合诱导的动物模型,从动物的学习记忆能力、糖脂代谢水平、海马神经细胞形态学变化等多功效途径综合评判,优选出最佳模型,并采用二甲双胍验证该模型.结果:(1)在学习记忆能力实验方面,D-半乳糖复合造模后,小鼠均较高糖组或高糖高脂组出现了典型的认知功能障碍,无论Morris水迷宫还是方形水迷宫,小鼠的逃避潜伏期时间明显延长,游到平台路径的错误次数明显增多;(2)在糖脂代谢实验方面,给予高糖高脂起着直观重要的作用.高脂高糖组和高糖高脂+D-半乳糖复合模型组,连续8w的血糖监测均较高糖组血糖变化幅度更小,模型稳定,血脂代谢也出现了明显的紊乱;(3)海马神经细胞形态学变化方面,高脂高糖组和高糖高脂+D-半乳糖复合模型组,小鼠海马组织较高糖组椎体细胞坏死和神经元空泡变性程度更为典型,均出现了明显的β淀粉样蛋白形成;(4)给予二甲双胍治疗后,上述症状均明显改善,模型验证成功.结论:综合上述结果和实验动物的死亡情况,以及节约试剂等多因素,采用高糖高脂+D-半乳糖(100mg/kg)复合连续造模8周(8 w)建立糖尿病认知功能障碍小鼠模型,方法学上是可行、可靠、可稳定的;同时,该模型也佐证了"糖脂毒"确实是造成糖尿病认知功能障碍的重要病机.
Objective：To study the core pathogenesis of diabetic cognitive dysfunction： the toxicity of glycolipid poison-induced brain damage, and the establishment of a stable and reliable model of diabetic cognitive dysfunction in diabetic mice from the di- alectical point of view in Chinese medicine. This model can provide scientific experimental tools for the study of preventing dia- betes and its complications in Chinese medicine and national medicine. Methods：To establish high glucose, high glucose and hyperlipidemia model and different doses of D-galactose ＋ high glucose and hyperlipidemia complex-induced animal models. The best model was selected based on multi-efficacious approach assessment from the learning and memory ability, the level of glu- cose and lipid metabolism, the morphological changes of hippocampal neurons of animals and so on. Results： （ 1 ） In the aspect of learning and memory ability,after making a model of D-galactose complex model,the mice in the higher sugar group or high glucose and hyperlipidemia group showed a typical cognitive dysfunction, regardless of Morris water maze or square water maze. The escape latency of mice was significantly prolonged,and the number of errors in finding the correct path of the platform was significantly increased; （2） In the experiment of glucose and lipid metabolism, high glucose and hyperlipidemia played an important role ; For hyperglycemia group and high glucose and hyperlipidemia ＋ D-galactose complex model group, the monitoring of the blood glucose level for 8w showed that the change range was smaller than that in the high glucose group, the model was stable and the dyslipidemia appeared obviously; （ 3 ） In terms of morphological changes of the nerve cells, for hyperglycemia group and high glucose and hyperlipidemia ＋ D-galactose complex model group, the ganglion cell necrosis and the vacuolar de- generation of the neurons in the hippocampus were more typical than the high glucose group,both presenting obvious formation of 13-amyl
出处
《西南民族大学学报（自然科学版）》
CAS
2017年第5期492-499,共8页
Journal of Southwest Minzu University(Natural Science Edition)
基金
国家自然科学基金(81302912)
中央高校基本科研业务费专项基金项目(2017NZYQN35)
西南民族大学大学生创新创业训练计划项目(X201710656129)
关键词
毒损脑络
糖尿病认知功能障碍
小鼠
疾病模型
damage of brain collateral by toxin
diabetic cognitive impairment
mice
disease model
