姜黄素对癫痫大鼠认知功能障碍的预防作用及其可能机制

Curcumin Attenuates Status Epilepticus-Induced Cognitive Deficits and the Possible Mechanism

目的:探讨姜黄素(curcumin)对癫痫大鼠认知功能障碍的预防作用及其可能机制。方法:将30只成年雄性SD大鼠分为正常对照组、单纯致痫组(SE组)、姜黄素[60mg/(kg.d)]干预组(curcumin组)。采用Morris水迷宫方法检测大鼠学习记忆功能变化,并检测脑片水平的长时程增强(LTP)变化,处死大鼠后取脑组织并匀浆,测超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)、谷胱甘肽(GSH)、丙二醛(MDA)的水平。结果:(1)SE组大鼠寻找平台的潜伏期明显长于对照组,具有统计学意义(P<0.05),姜黄素组寻找平台的潜伏期相对于SE组显著缩短(P<0.05)。撤离平台后,SE组大鼠在平台所在象限的停留时间明显短于对照组(P<0.05),姜黄素治疗后大鼠在平台所在象限的停留时间较SE组显著延长(P<0.05)。(2)给予HFS刺激后各组兴奋性突出后电位(fEPSP)斜率较前明显增加,均可持续1h以上,与对照组比较SE组HFS刺激后fEPSP斜率明显减小(P<0.05),姜黄素可减轻SE所致的fEPSP斜率减小(P<0.05)。(3)SE组SOD、GSH-PX、GSH显著下降,MDA明显增高,姜黄素可逆转上述现象,有统计学意义(P<0.05)。结论:姜黄素可显著减轻癫痫持续状态所致的大鼠认知功能障碍,减轻海马区的氧化应激反应从而保护海马海马是其可能机制之一。

Objective： The purpose of the study was to investigate the effect of curcumin on cognitive deficits induced by status epilepticus （SE） and the possible mechanism. Methods： The male SD rats were assigned to one of the following groups： （n =10 in each group）： Control group, SE group and Curcumin group. Cognitive function in 3 groups was tested by the water maze task. Hippocampal LTP was measured using patch-clamp recordings in rat brain slices. Glutathione（GSH） and Maleic Dialdehyde（MDA） content in the hippocampal homogenate were measured; The activity of Superoxide Dismutase （SOD） and glutathione peroxidase （GSH-PX）in the hippocampal homogenate were detected. Results： SE can cause severe cognitive deficits, and curcumin could attenuate SE-induced cognitive deficits. LTP inhibition in hippocampus caused by SE were markedly improved by administration of curcumin. Biochemical experiments revealed that SE can significantly increase content of MDA, decrease content of GSH and decreased the activities of SOD and GSH-PX in the hippocampal homogenate, which can be reversed by curcumin. Conclusions： Curcumin reveales therapeutic potential for SE-induced cognitive deficits, which is most likely related, at least in part, to its anti-oxidative stress actions in hippocampus.