目的：探讨糖尿病伴认知功能障碍大鼠模型的建立方法，并观察随着病程发展，糖尿病大鼠认知功能的变化。方法通过对SD大鼠腹腔注射高剂量链脲佐菌素（STZ）建立糖尿病大鼠模型，成模后在正常条件下饲养，采用Morris水迷宫观察第6、9、12周糖尿病大鼠的认知功能，光学显微镜和透射电子显微镜观察糖尿病大鼠海马神经元的形态学变化，了解糖尿病大鼠认知功能障碍形成的时间，确定认知功能障碍大鼠模型的建立方法。结果大鼠从发病后第6～12周，其认知功能障碍的程度随着糖尿病病程的延长呈进行性加重，海马神经元超微结构发生了明显改变，细胞器数量减少、细胞核深染，细胞开始凋亡；发病后第12周，海马组织切片 H E染色后光镜观察，可见其海马神经元数量明显减少，形态异常。结论随着糖尿病病程的延长，糖尿病大鼠可出现明显的认知功能障碍，至发病第12周，其大脑海马神经元在形态学上发生了明显变化，并出现了相应的行为学改变，因此可以将该时间段作为糖尿病并发认知功能障碍大鼠模型建立成功的时间。%Objective To analyze the mothdd of establishing diabetic rat model with cognitive dysfunction and observe the cognitive function change of diabetic rats with the development of the diabetes .Methods The SD rat model of type 1 diabetes melli‐tus(T1DM) was established by injecting of 50 mg/kg streptozotocin(STZ) and the T1DM rats′cognitive function by Morris water maze test in the six weeks ,9 weeks and 12 weeks was detected .In order to ascertain the time of appearing cognitive dysfunction in diabetic rats ,the morphological change of diabetic rats′ hippocampal neurons by optical microscope and the transmission electron microscopy were observed ,respectively .Results The degree of cognitive dysfunction of diabetic rats became gradually more serious from the 6th week to 12th week;the ultrastructure of hippocampal neurons have significantly changed and appeared apoptosis;the number of organelles decreased ,and the nucleus were dyed thickly ;the number of hippocampal neurons decreased obviously and the form of hippocampal neurons were abnormal observed by optical microscope in the twelfth week .Conclusion With the development of diabetes ,the diabetic rats could appear cognitive dysfunction obviously ,the forms of hippocampal neurons significantly change and appear the corresponding behavior changes in the twelveth week ,so this time is the time which the diabetic rat model with cog‐nitive dysfunction has been established successfully .
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