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精氨酸加压素激素受体拮抗剂在实验性自身免疫性脑脊髓炎啮齿动物模型中的应用:一种治疗人类多发性硬化症的新方法。

Arginine vasopressin hormone receptor antagonists in experimental autoimmune encephalomyelitis rodent models: A new approach for human multiple sclerosis treatment.

作者信息

Calvillo-Robledo Argelia, Ramírez-Farías Cynthia, Valdez-Urias Fernando, Huerta-Carreón Erika P, Quintanar-Stephano Andrés

机构信息

Departamento de Fisiología y Farmacología, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, Aguascalientes, Mexico.

出版信息

Front Neurosci. 2023 Mar 14;17:1138627. doi: 10.3389/fnins.2023.1138627. eCollection 2023.

DOI:10.3389/fnins.2023.1138627
PMID:36998727
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10043225/
Abstract

Multiple sclerosis (MS) is a chronic demyelinating and neurodegenerative disease that affects the central nervous system. MS is a heterogeneous disorder of multiple factors that are mainly associated with the immune system including the breakdown of the blood-brain and spinal cord barriers induced by T cells, B cells, antigen presenting cells, and immune components such as chemokines and pro-inflammatory cytokines. The incidence of MS has been increasing worldwide recently, and most therapies related to its treatment are associated with the development of several secondary effects, such as headaches, hepatotoxicity, leukopenia, and some types of cancer; therefore, the search for an effective treatment is ongoing. The use of animal models of MS continues to be an important option for extrapolating new treatments. Experimental autoimmune encephalomyelitis (EAE) replicates the several pathophysiological features of MS development and clinical signs, to obtain a potential treatment for MS in humans and improve the disease prognosis. Currently, the exploration of neuro-immune-endocrine interactions represents a highlight of interest in the treatment of immune disorders. The arginine vasopressin hormone (AVP) is involved in the increase in blood-brain barrier permeability, inducing the development and aggressiveness of the disease in the EAE model, whereas its deficiency improves the clinical signs of the disease. Therefore, this present review discussed on the use of conivaptan a blocker of AVP receptors type 1a and type 2 (V1a and V2 AVP) in the modulation of immune response without completely depleting its activity, minimizing the adverse effects associated with the conventional therapies becoming a potential therapeutic target in the treatment of patients with multiple sclerosis.

摘要

多发性硬化症(MS)是一种影响中枢神经系统的慢性脱髓鞘和神经退行性疾病。MS是一种多因素的异质性疾病,主要与免疫系统相关,包括由T细胞、B细胞、抗原呈递细胞以及趋化因子和促炎细胞因子等免疫成分诱导的血脑屏障和脊髓屏障的破坏。近年来,MS在全球的发病率一直在上升,并且与其治疗相关的大多数疗法都伴随着几种副作用的出现,如头痛、肝毒性、白细胞减少症以及某些类型的癌症;因此,人们一直在寻找有效的治疗方法。使用MS动物模型仍然是推断新治疗方法的重要选择。实验性自身免疫性脑脊髓炎(EAE)复制了MS发展的几种病理生理特征和临床症状,以获得针对人类MS的潜在治疗方法并改善疾病预后。目前,探索神经 - 免疫 - 内分泌相互作用是免疫疾病治疗领域的一个研究热点。精氨酸加压素(AVP)参与血脑屏障通透性的增加,在EAE模型中诱导疾病的发展和侵袭性,而其缺乏则可改善疾病的临床症状。因此,本综述讨论了使用1a型和2型AVP受体(V1a和V2 AVP)阻滞剂考尼伐坦来调节免疫反应,而不完全耗尽其活性,将与传统疗法相关的不良反应降至最低,从而成为治疗多发性硬化症患者的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bae/10043225/b0dadf446772/fnins-17-1138627-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bae/10043225/0081be85efe4/fnins-17-1138627-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bae/10043225/2ee4925b8efe/fnins-17-1138627-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bae/10043225/b0dadf446772/fnins-17-1138627-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bae/10043225/0081be85efe4/fnins-17-1138627-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bae/10043225/2ee4925b8efe/fnins-17-1138627-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bae/10043225/b0dadf446772/fnins-17-1138627-g003.jpg

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