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大麻二酚可减轻实验性自身免疫性脑脊髓炎发病高峰期脊髓微血管白细胞募集。

Cannabidiol Attenuates Leukocyte Recruitment to the Spinal Cord Microvasculature at Peak Disease of Experimental Autoimmune Encephalomyelitis.

机构信息

Núcleo de Neurociências, Programa de Pós-graduação em Ciências Biológicas:Fisiologia e Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, Universidade de Campinas, Campinas, Brazil.

出版信息

Cannabis Cannabinoid Res. 2024 Apr;9(2):537-546. doi: 10.1089/can.2022.0103. Epub 2023 Feb 6.

Abstract

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by neuroinflammation leading to demyelination. The associated symptoms lead to a devastating decrease in quality of life. The cannabinoids and their derivatives have emerged as an encouraging alternative due to their management of symptom in MS. The aim of the study was to investigate the mechanism of action of cannabidiol (CBD), a nonpsychoactive cannabinoid, on molecular and cellular events associated with leukocyte recruitment induced by experimental autoimmune encephalomyelitis (EAE). C57BL/6 female mice were randomly assigned to the four experimental groups: C (control group), CBD (cannabidiol-treated group, 5 mg/kg i.p.; 14 days), EAE (experimental autoimmune encephalomyelitis-induced group), and EAE+CBD (experimental autoimmune encephalomyelitis-induced plus cannabidiol-treated group). The results indicated that 5 mg/kg of CBD injected intraperitoneally between the 1st and 14th days of EAE could reduce the leukocyte rolling and adhesion into the spinal cord microvasculature as well cellular tissue infiltration. These results were supported by a decreased mRNA expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the spinal cord. Purified CBD reduces VCAM and ICAM-mediated leukocyte recruitment to the spinal cord microvasculature at EAE peak disease.

摘要

多发性硬化症(MS)是一种中枢神经系统的慢性自身免疫性疾病,其特征是神经炎症导致脱髓鞘。相关症状导致生活质量的严重下降。大麻素及其衍生物因其对 MS 症状的管理而成为一种令人鼓舞的替代方法。本研究旨在研究大麻二酚(CBD),一种非精神活性大麻素,对实验性自身免疫性脑脊髓炎(EAE)诱导的白细胞募集相关分子和细胞事件的作用机制。将 C57BL/6 雌性小鼠随机分配到四个实验组:C(对照组)、CBD(大麻二酚处理组,5mg/kg ip;14 天)、EAE(实验性自身免疫性脑脊髓炎诱导组)和 EAE+CBD(实验性自身免疫性脑脊髓炎诱导加大麻二酚处理组)。结果表明,EAE 第 1 天至第 14 天腹腔内注射 5mg/kg CBD 可减少白细胞滚动和黏附到脊髓微血管以及细胞组织浸润。这些结果得到了脊髓中细胞间黏附分子-1(ICAM-1)和血管细胞黏附分子-1(VCAM-1)mRNA 表达减少的支持。纯化的 CBD 可减少 VCAM 和 ICAM 介导的白细胞募集到 EAE 疾病高峰期的脊髓微血管。

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