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槲皮素对链脲佐菌素诱导的小鼠脑血流减少和记忆损伤的保护作用。

Protective effect of quercetin against intracerebral streptozotocin induced reduction in cerebral blood flow and impairment of memory in mice.

机构信息

Division of Pharmacology, Central Drug Research Institute, CSIR, Chattar Manzil, Lucknow, U.P., India.

出版信息

Behav Brain Res. 2010 May 1;209(1):73-9. doi: 10.1016/j.bbr.2010.01.017. Epub 2010 Jan 22.

Abstract

The aim of the present study is to investigate the effect of quercetin, a naturally occurring flavonoid, on cerebral blood flow (CBF), brain energy metabolism, memory impairment, oxidative stress and cholinergic dysfunction in brain following intracerebral (i.c.) streptozotocin (STZ) administration in mice. STZ (0.5mg/kg, i.c.) was administered twice at an interval of 48h. We found a significant reduction in CBF as measured by Laser Doppler Flowmetry (LDF). The brain energy metabolism was also altered as evidenced by significant reduction in brain ATP content. Daily treatment with quercetin (2.5, 5 and 10mg/kg, p.o.) starting from the first dose of STZ showed a dose-dependent restoration of CBF and ATP content. Further, quercetin prevented STZ induced memory impairment as assessed by Morris water maze and passive avoidance tests. Biochemical analysis revealed that STZ significantly increased malondialdehyde (MDA), nitrite and depleted glutathione (GSH) levels in the mice brain. Quercetin decreased oxidative and nitrosative stress as evidenced by a significant decrease in MDA, nitrite and increase in GSH levels. Quercetin also attenuated elevated acetylcholinesterase activity in the STZ-treated mice. Neither STZ (i.c.) nor quercetin showed any change in locomotor activity and blood glucose level. The present study demonstrates the beneficial effects of quercetin in improving CBF along with preventing memory impairment, oxidative stress, altered brain energy metabolism and cholinergic dysfunction caused by STZ in mice. Therefore, consumption of dietary stuff rich in quercetin should be encouraged to ward off dementia associated with vascular and neurodegenerative disorders.

摘要

本研究旨在探讨槲皮素(一种天然存在的类黄酮)对脑内(i.c.)链脲佐菌素(STZ)给药后小鼠大脑血流(CBF)、脑能量代谢、记忆障碍、氧化应激和胆碱能功能障碍的影响。STZ(0.5mg/kg,i.c.)在 48 小时的间隔内分两次给予。我们发现通过激光多普勒流量测定法(LDF)测量的 CBF 显著降低。大脑能量代谢也发生改变,表现为大脑 ATP 含量显著降低。从 STZ 的第一剂量开始,每天用槲皮素(2.5、5 和 10mg/kg,p.o.)治疗,显示出 CBF 和 ATP 含量的剂量依赖性恢复。此外,槲皮素可防止 STZ 诱导的莫里斯水迷宫和被动回避测试中的记忆障碍。生化分析显示,STZ 可显著增加小鼠大脑中的丙二醛(MDA)、亚硝酸盐和谷胱甘肽(GSH)水平。槲皮素降低氧化和亚硝化应激,表现为 MDA、亚硝酸盐显著减少和 GSH 水平增加。槲皮素还可减轻 STZ 处理小鼠中升高的乙酰胆碱酯酶活性。STZ(i.c.)或槲皮素均未引起小鼠的运动活动和血糖水平发生任何变化。本研究表明,槲皮素可改善 CBF,预防 STZ 引起的记忆障碍、氧化应激、改变的脑能量代谢和胆碱能功能障碍,从而对小鼠具有有益作用。因此,应该鼓励摄入富含槲皮素的饮食,以预防与血管和神经退行性疾病相关的痴呆症。

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