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目的探讨2型糖尿病(DM)是否加重慢性脑低灌注(CCH)大鼠胆碱能神经元及空间学习记忆能力损伤。方法 SD大鼠24只,随机分为4组(均n=6):①对照组(正常饮食+假手术);②DM组[高脂饮食+链脲佐菌素(STZ)];③CCH组[正常饮食+双侧颈总动脉永久性结扎(2-VO)];④DM-CCH组(高脂饮食+STZ+2-VO)。采用Morris水迷宫测试各组大鼠学习记忆能力;免疫组化学法检测海马区乙酰胆碱转移酶(ChAT)阳性细胞表达和免疫印迹法检测海马ChAT相对表达量。结果 DM+CCH组逃避潜伏期与对照组比较明显延长,第2~4天(P<0.001)、第5天(P<0.01);目标象限时间百分比明显低于对照组(P<0.01)、DM组(P<0.05)和CCH组(P<0.05)。DM+CCH组海马区ChAT阳性细胞表达明显减少,ChAT相对表达量较对照组显著减少(P<0.01)、DM组(P<0.05)和CCH组(P<0.05)显著减少。结论 DM可加重CCH大鼠的空间学习记忆能力障碍,可能与海马区胆碱能神经元损伤有关。
Objective To investigate whether type 2 diabetes mellitus (DM) aggravates cholinergic neurons and spatial learning and memory abilities in rats with chronic cerebral hypoperfusion (CCH). Methods Twenty-four SD rats were randomly divided into four groups (n = 6 each): ① control group (normal diet + sham operation); ② DM group [hypercholesterolemia + streptozotocin (STZ) Normal diet + permanent bilateral carotid artery ligation (2-VO)]; ④DM-CCH group (high-fat diet + STZ + 2-VO). Morris water maze was used to test the learning and memory abilities of rats in each group. The expression of ChAT in hippocampus was detected by immunohistochemistry and the relative expression of ChAT in hippocampus was detected by Western blotting. Results The escape latency of DM + CCH group was significantly longer than that of the control group (P <0.001) on day 2 and 5 (P <0.01), and the percentage of target quadrant time was significantly lower than that of control group (P <0.01) Group (P <0.05) and CCH group (P <0.05). The expression of ChAT in hippocampus of DM + CCH group was significantly lower than that in control group (P <0.01), but the level of ChAT in DM + CCH group was significantly decreased (P <0.05). Conclusion DM can aggravate the spatial learning and memory dysfunction in CCH rats, which may be related to the damage of cholinergic neurons in hippocampus.