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大麻二酚在子宫内膜异位症相关炎症和氧化过程管理中的分子和生化机制。

Molecular and Biochemical Mechanism of Cannabidiol in the Management of the Inflammatory and Oxidative Processes Associated with Endometriosis.

机构信息

Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres 31, 98166 Messina, Italy.

Department of Biomedical, Dental and Morphological and Functional Imaging, University of Messina, Via Consolare Valeria, 98125 Messina, Italy.

出版信息

Int J Mol Sci. 2022 May 12;23(10):5427. doi: 10.3390/ijms23105427.

DOI:10.3390/ijms23105427
PMID:35628240
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9141153/
Abstract

Endometriosis is usually associated with inflammation and chronic pelvic pain. This paper focuses the attention on the anti-inflammatory, anti-oxidant and analgesic effects of cannabidiol (CBD) and on its potential role in endometriosis. We employed an in vivo model of endometriosis and administered CBD daily by gavage. CBD administration strongly reduced lesions diameter, volume and area. In particular, it was able to modify lesion morphology, reducing epithelial glands and stroma. CBD showed anti-oxidant effects reducing lipid peroxidation, the expression of Nox-1 and Nox-4 enzymes. CBD restored the oxidative equilibrium of the endogenous cellular defense as showed by the SOD activity and the GSH levels in the lesions. CBD also showed important antifibrotic effects as showed by the Masson trichrome staining and by downregulated expression of MMP-9, iNOS and TGF-β. CBD was able to reduce inflammation both in the harvested lesions, as showed by the increased Ikb-α and reduced COX2 cytosolic expressions and reduced NFkB nuclear localization, and in the peritoneal fluids as showed by the decreased TNF-α, PGE2 and IL-1α levels. CBD has important analgesic effects as showed by the reduced mast cells recruitment in the spinal cord and the reduced release of neuro-sensitizing and pro-inflammatory mediators. In conclusion, the collected data showed that CBD has an effective and coordinated effects in endometriosis suppression.

摘要

子宫内膜异位症通常与炎症和慢性盆腔疼痛有关。本文重点关注大麻二酚 (CBD) 的抗炎、抗氧化和镇痛作用及其在子宫内膜异位症中的潜在作用。我们采用了子宫内膜异位症的体内模型,并通过灌胃每天给予 CBD。CBD 给药强烈降低了病变的直径、体积和面积。特别是,它能够改变病变的形态,减少上皮腺和基质。CBD 表现出抗氧化作用,降低脂质过氧化、Nox-1 和 Nox-4 酶的表达。CBD 通过在病变中恢复 SOD 活性和 GSH 水平来恢复内源性细胞防御的氧化平衡。CBD 还表现出重要的抗纤维化作用,如 Masson 三色染色所示,以及 MMP-9、iNOS 和 TGF-β 的表达下调。CBD 能够减少收获的病变中的炎症,如 Ikb-α 的增加和 COX2 细胞质表达的减少以及 NFkB 核定位的减少,以及腹腔液中的炎症,如 TNF-α、PGE2 和 IL-1α 水平的降低。CBD 具有重要的镇痛作用,如脊髓中肥大细胞募集的减少和神经敏化和促炎介质释放的减少。总之,收集的数据表明 CBD 在抑制子宫内膜异位症方面具有有效且协调的作用。

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