葡萄糖-PEG_(2000)-DSPE修饰卡马西平纳米系统对癫痫大鼠海马线粒体内氧化应激作用  

Effect of Glucose-PEG_(2000)-DSPE Modified Carbamazepine Nanosystem on Oxidative Stress in Hippocampal Mitochondria of Epileptic Rats

作　　者：赵斐[1] 谢旭芳 吴成斯[1] 梁慧婷[1] ZHAO Fei;XIE Xufang;WU Chengsi;LIANG Huiting(The First Affiliated Hospital of Nanchang University,Nanchang Jiangxi 330006,China)

机构地区：[1]南昌大学第一附属医院,江西南昌330006

出　　处：《药品评价》2023年第9期1074-1077,共4页Drug Evaluation

基　　金：江西省卫生健康委员会科技计划项目(202130153);江西省教育厅科学技术研究项目(GJJ200166)

摘　　要：目的基于癫痫大鼠海马神经细胞中线粒体内氧化应激机制,探究葡萄糖(GLU)-PEG_(2000)-DSPE修饰卡马西平纳米系统脑靶向效果。方法制备GLU-PEG_(2000)-DSPE修饰卡马西平纳米系统,观察纳米粒子的表面形态,检测不同浓度卡马西平纳米粒子的毒性作用。大鼠随机分为正常组、模型组、卡马西平组、纳米组,除正常组外,其余三组大鼠均构建癫痫大鼠模型。检测卡马西平在癫痫大鼠脑部的蓄积情况,分析卡马西平对各组大鼠海马组织的病理形态和超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)含量的影响。结果100μg/mL卡马西平纳米粒子溶液对神经元细胞存活率的影响高于100μg/mL单纯的卡马西平溶液(P<0.05)。卡马西平纳米组大鼠脑组织中卡马西平含量(1.69±0.17)μg/mL明显高于卡马西平组大鼠脑组织中卡马西平含量(1.02±0.10)μg/mL(P<0.05)。卡马西平组、纳米组大鼠海马组织病理形态相较于模型组均有所改善,且纳米组大鼠改善效果更佳。与模型组相比,卡马西平组、纳米组大鼠海马组织中SOD、GSH-Px含量明显上升,MDA含量明显下降(P<0.05)。与卡马西平组相比,纳米组大鼠海马组织中SOD、GSH-Px含量明显上升,MDA含量明显下降(P<0.05)。结论GLU-PEG_(2000)-DSPE修饰卡马西平纳米系统可以有效改善癫痫大鼠海马组织的病理状态,缓解其氧化应激损伤。Objective Based on the mechanism of oxidative stress in mitochondria in hippocampal neurons of epileptic rats,the brain targeting effect of glucose(GLU)PEG_(2000)-DSPE modified carbamazepine nanosystem was investigated.Methods GLU-PEG_(2000)-DSPE modified carbamazepine nanosystem was prepared,the surface morphology of nanoparticles was observed,and the toxicity of carbamazepine nanoparticles with different concentrations was detected.The rats were randomly divided into normal group,model group,carbamazepine group and nano group.Except the normal group,the epileptic rat model was established in the other three groups.The accumulation of carbamazepine in the brain of epileptic rats was detected,and the effects of carbamazepine on the pathological morphology and the content of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and malonaldehyde(MDA)in hippocampal tissues of rats in each group were analyzed.Results The effect of 100μg/mL carbamazepine nanoparticle solution on neuronal cell survival rate was higher than that of 100μg/mL simple carbamazepine solution(P<0.05).The content of carbamazepine(1.69±0.17)μg/mL in brain tissue of carbamazepine group was significantly higher than that of carbamazepine group(1.02±0.10)μg/mL(P<0.05).Compared with the model group,the hippocampal histological morphology in carbamazepine group and nano group was improved,and the nano group was better.Compared with model group,SOD and GSH-Px contents in hippocampal tissue of carbamazepine group and nano group were significantly increased,while MDA content was significantly decreased(P<0.05).Compared with carbamazepine group,the contents of SOD and GSH-Px in hippocampus of rats in nano group were significantly increased,while the content of MDA was significantly decreased(P<0.05).Conclusion GLU-PEG_(2000)-DSPE modified carbamazepine nanosystem can effectively improve the pathological state of hippocampal tissue in epileptic rats and alleviate oxidative stress damage.

关 键 词：卡马西平 靶向纳米粒子 癫痫 氧化应激 SD大鼠 

分 类 号：R742.1[医药卫生—神经病学与精神病学]