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纳米壳聚糖包被的大麻二酚对阿尔茨海默病大鼠模型学习记忆、海马 CB1 和 CB2 水平及淀粉样斑块的影响。

The Effect of Cannabidiol Coated by Nano-Chitosan on Learning and Memory, Hippocampal CB1 and CB2 Levels, and Amyloid Plaques in an Alzheimer's Disease Rat Model.

机构信息

Department of Pharmacology, Karaj Branch, Islamic Azad University, Karaj, Iran.

出版信息

Neuropsychobiology. 2022;81(3):171-183. doi: 10.1159/000519534. Epub 2021 Nov 2.

Abstract

INTRODUCTION

Using nanoparticle (NP) drugs can have better effects on the target tissue in various diseases. Alzheimer's disease (AD) is one of the degenerative neurological diseases that due to its high prevalence, requires the use of more appropriate treatments. Therefore, the aim of this study was consideration of the effect of cannabidiol (CBD) coated by nano-chitosan on learning and memory, hippocampal cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 1 (CB2) levels, and amyloid plaques in an AD rat model.

MATERIAL AND METHODS

Thirty-five male Wistar rats were randomly divided into 5 groups (n = 7 in each): control, Alzheimer's disease model that received the beta-amyloid (Aβ) peptide (Alz), Alz + nano-chitosan (NP) Alz + CBD, and Alz + NP + CBD. Alz was induced by injection of the Aβ1-42 peptide into the hippocampal area cornu ammonis1. After confirmation of Alz, 1 μL of CBD and NP + CBD were administered by oral gavage daily in rats for 1 month. The Morris water maze (MWM) test was used to assess learning and memory of animals. Cresyl violet staining was used for consideration of dead cells. Gene and protein expression of CB1 and CB2 was performed by real-time PCR and immunohistochemistry methods.

RESULTS

Induction of Alz significantly increased Aβ plaques and dead cells compared to the control group (p < 0.001). Results of MWM in the day test show that Alz + NP + CBD significantly decrease escape latency (p < 0.01), travelled distance (p < 0.001), and significantly increased spending time (p < 0.001) compared to the Alz group. Protein expression of CB1 and CB2 significantly increased in Alz + CBD and Alz + NP + CBD compared to the Alz group (p < 0.05).

CONCLUSION

It seems that CBD coated by nano-chitosan has good potential for reducing Aβ plaques, increasing brain CB1 and levels CB2, and improving learning and memory in Alz rats.

摘要

介绍

使用纳米粒子(NP)药物可以在各种疾病中对目标组织产生更好的效果。阿尔茨海默病(AD)是一种退行性神经疾病,由于其高发病率,需要使用更合适的治疗方法。因此,本研究的目的是研究纳米壳聚糖包裹的大麻二酚(CBD)对 AD 大鼠模型学习和记忆、海马大麻素受体 1 型(CB1)和大麻素受体 2 型(CB2)水平以及淀粉样斑块的影响。

材料和方法

35 只雄性 Wistar 大鼠随机分为 5 组(每组 7 只):对照组、接受β-淀粉样蛋白(Aβ)肽(Alz)的 AD 模型组、Alz+纳米壳聚糖(NP)组、Alz+CBD 组和 Alz+NP+CBD 组。通过向海马角 1 区注射 Aβ1-42 肽诱导 Alz。在确认 Alz 后,每天通过口服灌胃给予大鼠 1 μL 的 CBD 和 NP+CBD,持续 1 个月。通过 Morris 水迷宫(MWM)测试评估动物的学习和记忆。使用 Cresyl 紫染色法考虑死亡细胞。通过实时 PCR 和免疫组织化学方法检测 CB1 和 CB2 的基因和蛋白表达。

结果

与对照组相比,Alz 诱导显著增加了 Aβ 斑块和死亡细胞(p < 0.001)。MWM 日测试结果表明,与 Alz 组相比,Alz+NP+CBD 组显著降低了逃避潜伏期(p < 0.01)、行进距离(p < 0.001),并显著增加了停留时间(p < 0.001)。与 Alz 组相比,Alz+CBD 和 Alz+NP+CBD 组 CB1 和 CB2 的蛋白表达显著增加(p < 0.05)。

结论

纳米壳聚糖包裹的 CBD 具有减少 Aβ 斑块、增加大脑 CB1 和 CB2 水平以及改善 Alz 大鼠学习和记忆的潜力。

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