Can Özgür Devrim, Ulupınar Emel, Özkay Ümide Demir, Yegin Bengi, Öztürk Yusuf
Department of Pharmacology, Faculty of Pharmacy, Anadolu University, Eskisehir, Turkey.
Behav Pharmacol. 2012 Sep;23(5-6):582-92. doi: 10.1097/FBP.0b013e328356c3f2.
The aim of this study was to examine the effect of simvastatin (SMV), a 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor, in rats fed with a standard or a high-fat diet (HFD) throughout the prenatal and the postnatal periods. The emotional status of the animals was evaluated by elevated plus-maze and modified forced swimming tests, whereas cognitive performance was assessed by a Morris water maze task. Morphological changes in the hippocampus were examined by design-based stereology. HFD exposure significantly increased blood serum triglycerides without altering cholesterol levels relative to the controls. After four weeks of oral SMV (5 mg/kg) administration, serum triglycerides reverted to the control level. SMV caused significant anxiolytic, antidepressant-like, and nootropic effects in animals fed the standard diet. In the HFD group, enhanced anxiety and depression, and reduced cognitive performances of animals were reversed by SMV treatment. Although a total volume estimation of the hippocampal subfields indicated no significant change among the groups, the total number of pyramidal neurons decreased significantly in animals fed the HFD; following SMV treatment, this detrimental effect was reversed. In conclusion, chronic SMV administration has significant therapeutic potential for the treatment of affective and cognitive disorders with or without altering the serum lipid profiles.
本研究的目的是考察辛伐他汀（SMV），一种3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂，在产前和产后全程给予标准饮食或高脂饮食（HFD）大鼠中的作用。通过高架十字迷宫和改良强迫游泳试验评估动物的情绪状态，而通过莫里斯水迷宫任务评估认知能力。采用基于设计的体视学方法检测海马体的形态变化。与对照组相比，高脂饮食暴露显著增加血清甘油三酯水平，而胆固醇水平未改变。口服SMV（5mg/kg）四周后，血清甘油三酯恢复到对照水平。SMV对喂食标准饮食的动物具有显著的抗焦虑、抗抑郁样和促智作用。在高脂饮食组中，SMV治疗可逆转动物增强的焦虑和抑郁以及降低的认知能力。虽然海马体亚区的总体积估计显示各组间无显著变化，但喂食高脂饮食的动物锥体神经元总数显著减少；SMV治疗后，这种有害作用得到逆转。总之，长期给予SMV对治疗伴有或不伴有血清脂质谱改变的情感和认知障碍具有显著的治疗潜力。
