SIMVASTATIN AMELIORATES MEMORY IMPAIRMENT AND NEUROTOXICITY IN STREPTOZOTOCIN-INDUCED DIABETIC MICE
SIMVASTATIN AMELIORATES MEMORY IMPAIRMENT AND NEUROTOXICITY IN STREPTOZOTOCIN-INDUCED DIABETIC MICE
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辛伐他汀可改善链脲佐菌素诱发的糖尿病小鼠的记忆损伤和神经毒性
DOI：
10.1016/j.neuroscience.2017.05.001
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发表时间：
2017-07-04
期刊：
影响因子：
3.3
通讯作者：
Tang, Su-Su
中科院分区：
文献类型：
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作者：
Fang, Shun-Chang;Xie, Hang;Tang, Su-Su
糖尿病伴随着中度至重度高脂血症的额外负担，但关于降脂治疗对糖尿病并发症（如糖尿病相关认知功能下降）的影响知之甚少。在此，我们研究了他汀类药物对链脲佐菌素诱导的糖尿病小鼠记忆障碍和神经毒性的影响。我们的数据表明，口服辛伐他汀10或20 mg/kg 4周显着改善糖尿病相关的记忆障碍，反映在Morris水迷宫和Y-迷宫测试中的性能更好。进一步的研究表明，这些治疗引起海马和皮质核中过氧化物酶体增殖物激活受体γ的显著增加和NF-κ B p65的减少，并改善神经炎症反应，如较少的Iba-1阳性细胞和较低的炎症介质包括IL-β、IL-6和TNF-α，以及抑制神经元凋亡，如减少的TUNEL阳性细胞所示，海马和皮质Bcl-2/Bax比值升高，caspase-3活性降低。此外，辛伐他汀通过降低淀粉样蛋白-β、淀粉样蛋白前体蛋白（APP）和β位点APP裂解酶-1显著减弱淀粉样蛋白生成。正如预期的那样，用辛伐他汀治疗，糖尿病小鼠表现出高脂血症而不是高血糖症的显著改善。我们的研究结果揭示了辛伐他汀对糖尿病相关认知功能障碍的新的治疗潜力。(C)2017年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Diabetes comes with an additional burden of moderate to severe hyperlipidemia, but little is known about the effects of lipid-lowering therapy on diabetic complications such as diabetes-associated cognitive decline. Herein we investigated the effects of statins on memory impairment and neurotoxicity in streptozotocin-induced diabetic mice. Our data indicated that oral administration of simvastatin at 10 or 20 mg/kg for 4 weeks significantly ameliorated diabetes-associated memory impairment reflected by performance better in the Morris water maze and Y-maze tests. The further study showed that these treatments caused significant increase of peroxisome proliferator-activated receptors gamma and decrease of NF-kappa B p65 in nucleus of hippocampus and cortex, and ameliorated neuroinflammatory response as evidenced by less Iba-1-positive cells and lower inflammatory mediators including IL-beta,IL-6 and TNF-alpha as well as suppressed neuronal apoptosis as indicated by decreased TUNEL-positive cells, increased ratio of Bcl-2/Bax and decreased caspase-3 activity in the hippocampus and cortex. Moreover, simvastatin pronouncedly attenuated amyloidogenesis by decreasing amyloid-beta, amyloid precursor protein (APP) and beta-site APP cleaving enzyme-1. As expected, treated with simvastatin, the diabetic mice exhibited significant improvement of hyperlipidemia rather than hyperglycemia. Our findings disclosed novel therapeutic potential of simvastatin for the diabetes associated cognitive impairment. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.