全谱大麻二酚油治疗可改善营养不良突变小鼠的病理表现。

IF 2.8 3区医学 Q2 CLINICAL NEUROLOGY

Muscle & Nerve Pub Date : 2025-01-22 DOI:10.1002/mus.28337

Laís Leite Ferreira, Fabricio Souza Gomes, Beatriz Godinho Nascimento, Wagner Corsini, Luis Felipe Cunha Dos Reis, João Marcos Oliveira-Silva, Josie Resende Torres da Silva, Marcelo Lourenço da Silva, Angel Maurício Castro Gamero, Túlio de Almeida Hermes

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引用次数: 0

摘要

简介/目的：杜氏肌营养不良症（DMD）是由DMD基因的致病变异引起的，使肌纤维容易受到收缩引起的膜损伤。鉴于大麻二酚（CBD）的潜在有益作用，我们评估了全谱CBD油对营养不良肌纤维活力的体外影响以及对mdx小鼠（DMD模型）肌病的体内影响。方法：在体外用全谱CBD油处理mdx小鼠的营养不良细胞，并进行细胞活力和细胞毒性分析。在体内，14日龄mdx小鼠接受10 mg/kg/天的全谱CBD油，持续14天。我们分析了肌酸激酶（CK）水平、肝损伤标志物以及膈肌（DIA）和股四头肌的组织病理学（QUA [IgG阳性染色的肌坏死纤维、再生纤维/中央核、最小Feret直径、纤维化区、炎症区、巨噬细胞的存在和nf - κ B含量]）。结果：全谱CBD油体外处理具有剂量依赖性的细胞毒作用；然而，体内10 mg/kg治疗安全有效地改善了DIA和QUA的DMD组织病理学评估参数：中央核减少：1.7%±2.0%对22.4%±5.3%和11.1%±10.7%对32.3%±4.6%；减少免疫球蛋白g +肌纤维:0.6%±0.7%和8.4%±1.6%和0.9%±0.3%和7.5%±1.0%;肌纤维大小增加：85.2±3.2 μm vs 64.3±4.0 μm; 106.5±8.6 μm vs 81.2±4.8 μm；炎症面积减少：6.2%±2.7%对15.1%±2.6%,5.3±4.1对17.3%±2.8%；减少巨噬细胞面积:0.05%±0.1%和10.8%±4.3%和1.0%±0.7%和10.3%±4.9%;NF -κB含量:0.6%±0.1%和1.7%±0.2%和1.7%±0.1%和5.2%±2.1%;和纤维化:5.6%±1.8%和12.0%±3.7%和1.3%±0.5%和4.7%±1.5%。它还降低了血清CK。讨论：全谱CBD油可能代表了一种治疗DMD的有希望的新方法，但必须考虑其潜在的毒性。

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Treatment With Full-Spectrum Cannabidiol Oil Improved the Pathological Findings of Dystrophic Mutant Mice.

Introduction/aims: Duchenne muscular dystrophy (DMD) is caused by pathogenic variants in the DMD gene, making muscle fibers susceptible to contraction-induced membrane damage. Given the potential beneficial action of cannabidiol (CBD), we evaluated the in vitro effect of full-spectrum CBD oil on the viability of dystrophic muscle fibers and the in vivo effect on myopathy of the mdx mouse, a DMD model.

Methods: In vitro, dystrophic cells from the mdx mouse were treated with full-spectrum CBD oil and assessed with cell viability and cytotoxic analyses. In vivo, fourteen-day-old mdx mice received 10 mg/kg/day of the full-spectrum CBD oil for 14 days. We analyzed creatine kinase (CK) levels, liver damage markers, and histopathology of the diaphragm (DIA) and quadriceps (QUA [myonecrotic fibers with positive IgG staining, regenerated fibers/central nuclei, the minimum Feret's diameter, the fibrosis area, the inflammatory area, the presence of macrophages, and NF-kappa B content]).

Results: In vitro treatment with full-spectrum CBD oil showed a dose-dependent cytotoxic effect; however, in vivo 10 mg/kg treatment was safe and effectively improved DMD histopathological assessment parameters in DIA and QUA: reduction of central nuclei: 1.7% ± 2.0% versus 22.4% ± 5.3% and 11.1% ± 10.7% versus 32.3% ± 4.6%; reduction of IgG+ myofibers: 0.6% ± 0.7% versus 8.4% ± 1.6% and 0.9% ± 0.3% versus 7.5% ± 1.0%; increase in myofiber size: 85.2 ± 3.2 versus 64.3 ± 4.0 μm and 106.5 ± 8.6 versus 81.2 ± 4.8 μm; decrease in inflammatory area: 6.2% ± 2.7% versus 15.1% ± 2.6% and 5.3 ± 4.1 versus 17.3% ± 2.8%; reduced macrophage area: 0.05% ± 0.1% versus 10.8% ± 4.3% and 1.0% ± 0.7% versus 10.3% ± 4.9%; NF-κB levels: 0.6% ± 0.1% versus 1.7% ± 0.2% and 1.7% ± 0.1% versus 5.2% ± 2.1%; and fibrosis: 5.6% ± 1.8% versus 12.0% ± 3.7% and 1.3% ± 0.5% versus 4.7% ± 1.5%. It also reduced serum CK.

Discussion: Full-spectrum CBD oil may represent a promising new approach to treating DMD, but its potential toxicity must be considered.

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来源期刊

Muscle & Nerve 医学-临床神经学

CiteScore

6.40

自引率

5.90%

发文量

287

审稿时长

3-6 weeks

期刊介绍： Muscle & Nerve is an international and interdisciplinary publication of original contributions, in both health and disease, concerning studies of the muscle, the neuromuscular junction, the peripheral motor, sensory and autonomic neurons, and the central nervous system where the behavior of the peripheral nervous system is clarified. Appearing monthly, Muscle & Nerve publishes clinical studies and clinically relevant research reports in the fields of anatomy, biochemistry, cell biology, electrophysiology and electrodiagnosis, epidemiology, genetics, immunology, pathology, pharmacology, physiology, toxicology, and virology. The Journal welcomes articles and reports on basic clinical electrophysiology and electrodiagnosis. We expedite some papers dealing with timely topics to keep up with the fast-moving pace of science, based on the referees'' recommendation.