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载姜黄素壳聚糖-海藻酸钠-STPP 纳米粒改善戊四氮点燃癫痫模型的记忆障碍和减少神经胶质细胞激活。

Curcumin-loaded chitosan-alginate-STPP nanoparticles ameliorate memory deficits and reduce glial activation in pentylenetetrazol-induced kindling model of epilepsy.

机构信息

Student Research Committee, Babol University of Medical Sciences, Babol, Mazandaran, Iran.

Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Mazandaran, Iran; Neuroscience Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Mazandaran, Iran.

出版信息

Prog Neuropsychopharmacol Biol Psychiatry. 2017 Oct 3;79(Pt B):462-471. doi: 10.1016/j.pnpbp.2017.07.025. Epub 2017 Aug 1.

Abstract

Despite several beneficial effects of curcumin, its medical application has been hampered due to low water solubility. To improve the aqueous solubility of curcumin, it has been loaded on chitosan (CS)-alginate (ALG) - sodium tripolyphosphate (STPP) nanoparticles (NPs). Then, the effect of curcumin NPs on memory improvement and glial activation was investigated in pentylenetetrazol (PTZ)-induced kindling model. Male NMRI mice have received the daily injection of curcumin NPs at dose of 12.5 or 25mg/kg. All interventions were injected intraperitoneally (i.p), 10days before PTZ administration and the injections were continued until 1h before each PTZ injection. Spatial learning and memory was evaluated using Morris water maze test after the 7th PTZ injection. Animals have received 10 injections of PTZ and then, brain tissues were removed for histological evaluation. Nissl staining was used to determine the level of cell death in hippocampus and immunostaining method was performed against NeuN and GFAP/Iba1 for assessment of neuronal density and glial activation respectively. Behavioral results showed that curcumin NPs exhibit anticonvulsant activity and prevent cognitive impairment in fully kindled animals. The level of cell death and glial activation reduced in animals which have received curcumin NPs compared to those received free curcumin. To conclude, these findings suggest that curcumin NPs effectively ameliorate memory impairment and attenuate the level of activated glial cells in a mice model of chronic epilepsy.

摘要

尽管姜黄素具有多种有益作用,但由于其水溶性低,其医学应用受到了阻碍。为了提高姜黄素的水溶性,已将其负载于壳聚糖(CS)-海藻酸钠(ALG)-三聚磷酸钠(STPP)纳米颗粒(NPs)上。然后,研究了姜黄素 NPs 对戊四氮(PTZ)诱导的点燃模型中记忆改善和神经胶质细胞激活的影响。雄性 NMRI 小鼠每天接受姜黄素 NPs 注射,剂量为 12.5 或 25mg/kg。所有干预均经腹腔(i.p)注射,在 PTZ 给药前 10 天开始,并在每次 PTZ 注射前 1 小时继续注射。在第 7 次 PTZ 注射后,使用 Morris 水迷宫测试评估空间学习和记忆。动物接受了 10 次 PTZ 注射,然后取出脑组织进行组织学评估。尼氏染色用于确定海马体中的细胞死亡水平,免疫染色方法用于评估神经元密度和神经胶质细胞激活的 NeuN 和 GFAP/Iba1。行为学结果表明,姜黄素 NPs 具有抗惊厥活性,并可预防完全点燃动物的认知障碍。与接受游离姜黄素的动物相比,接受姜黄素 NPs 的动物的细胞死亡和神经胶质细胞激活水平降低。总之,这些发现表明姜黄素 NPs 可有效改善慢性癫痫小鼠模型的记忆障碍,并减轻激活的神经胶质细胞水平。

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