糖尿病合并脑缺血再灌注导致学习记忆障碍大鼠模型的建立

Animal model of cognitive impairment induced by cerebral ischemia reperfusion in diabetic rats

目的建立糖尿病合并脑缺血再灌注导致学习记忆障碍大鼠模型。方法Wistar大鼠70只,分为正常对照组,糖尿病+假手术组,脑缺血组,糖尿病+脑缺血组。腹腔注射链脲佐菌素建立糖尿病模型,3d后双侧颈总动脉夹阻再灌注2次。术后1个月用跳台和Morris水迷宫判断其学习记忆能力,取海马组织,HE染色观察CA1区的细胞分布。结果电击后5min模型组的被动回避反应下台潜伏期明显缩短(P<0.01),24h后仍小于其他各组(P<0.05)。模型组学会主动回避反应的训练次数显著多于其他3组(P<0.001)。模型组在目标象限停留的时间最短(P<0.01),游泳的距离也最短(P<0.05)。结论糖尿病合并脑缺血再灌注可在短期内造成学习记忆障碍,糖尿病可加重脑缺血造成的脑损伤。

Objective To prepare a novo model of cognitive impairment induced by cerebral ischemia reperfusion in diabetic rats. Methods Seventy female Wistar rats were randomly divided into 4 groups ： normal control group, ischemic group, diabetic sham-operation group and diabetic iscbemic group. Streptozotocin was injected i. p. at a dose of 60 mg/kg, 3 days before the preparation of experimental iscbemia. The method used to produce cerebral ischemia was the two-vessel occlusion followed by re-pedusion. After 1-month recovery the animal model with cognitive impairment was confirmed by behavioral assessment. Learning and memorial behaviors of the rats were investigated by a passive and active avoidance response tests and a spatial version of the Morris water maze test. Neuron loss in the area of hippocampus was determined by the pathological H-E staining method. Results The performance of passive avoidance in diabetic cerebral iscbemia reperfusion was significantly impaired. The step-down latency of the passive avoidance response of the model rats was shorter, especially at 5th min after training （P 〈0. 01 ）. In active avoidance training, the training times of the model group were significantly more than that of the other three groups （P 〈0. 001）. The swimming time of the rats in Morris water maze in model group was significantly shorter than that in other groups （P 〈0. 01 ）. The swimming distance of rats in model group was the shortest among all 4 groups（ P 〈 0. 05 ）. Conclusion The cognitive ability in diabetic rats with cerebral ischemia 30 days after being induced was significantly declined as compared with the other three groups and diabetes can promote neuronal damage of the brain via cerebral ischemia.