1型糖尿病模型小鼠空间学习记忆障碍及海马组织氧化应激的变化

Impairment of spatial learning and memory and changes of oxidative stress in hippocampus from Type 1 diabetic mice

目的:探讨1型糖尿病模型小鼠空间学习记忆功能障碍与海马组织诱导型一氧化氮合酶(inducible nitric oxide synthase,i NOS)活性、超氧化物歧化酶(superoxide dismutase,SOD)活性及丙二醛(malondiadehyde,MDA)含量变化的关系。方法:将60只雄性FVB-Tg(Gad GFP)4570Swn/J小鼠随机分为对照组(NC组,n=20)和1型糖尿病模型组(DM组,n=40)。采用链脲佐菌素(100 mg/kg)诱导1型糖尿病小鼠模型,用Morris水迷宫行为学实验检测小鼠空间学习及记忆能力(逃避潜伏期、目的象限内徘徊时间、穿越平台次数),测定DM组中选出的空间学习和记忆能力最差的20只小鼠(糖尿病脑病小鼠)和NC组小鼠海马组织中i NOS活性、SOD活性及MDA含量。结果:链脲佐菌素腹腔注射后12周,与NC组比,DM组小鼠逃避潜伏期延长(P<0.01),在目的象限内徘徊时间和穿越平台次数减少(P<0.01),小鼠空间学习和记忆能力明显受损;糖尿病脑病小鼠海马组织中i NOS活性及MDA含量明显增高,SOD活性明显降低(P<0.01)。结论:小鼠海马组织中氧化应激明显增加可能是引发1型糖尿病脑病认知功能障碍的因素之一。

Objective： To investigate the relevance between spatial learning and memory impairment and the changes of inducible nitric oxide synthase （iNOS） activity, superoxide dismutase （SOD） activity and malondiadehyde （MDA） content in hippocampus from Type 1 diabetic mice. Methods： Sixty male mice were randomly assigned into a control group （NC group, 20 mice） and a Type 1 diabetic group （DM group, 40 mice）. Type 1 diabetic mouse models were established by a large dose intraperitoneal injection of streptozotocin （100 mg/kg）. The spatial learning and memory abilities of mice were assessed by Morris water maze （MWM） test. After MWM test, we chose 20 mice （diabetic encephalopathy mice） with the worst spatial learning and memory abilities from diabetic model group, and detected the iNOS activity, SOD activity and MDA content in hippocampus in both groups. Results： Compared with the NC group, the escape latency was significantly extended and platform crossings were significantly declined in diabetic mice （P〈0.01）. Furthermore, the activity of iNOS and the content of MDA were markedly increased, and the activity of SOD was significantly decreased in hippocampus of diabetic encephalopathy mice （P〈0.01）.Conclusion： The established Type 1 diabetic mice show symptoms of cognitive dysfunction, which might be related to the increase of oxidative stress in hippocampus.