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精氨酸加压素与 COVID-19 的病理生理学:一种创新视角。

Arginine vasopressin and pathophysiology of COVID-19: An innovative perspective.

机构信息

Department of Clinical Pharmacology and Medicine, College of Medicine, ALmustansiriyia University, Baghdad, Iraq.

Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.

出版信息

Biomed Pharmacother. 2021 Nov;143:112193. doi: 10.1016/j.biopha.2021.112193. Epub 2021 Sep 15.

Abstract

In Covid-19, systemic disturbances may progress due to development of cytokine storm and dysregulation of and plasma osmolarility due to high release of pro-inflammatory cytokines and neuro-hormonal disorders. Arginine vasopressin (AVP) which is involve in the regulation of body osmotic system, body water content, blood pressure and plasma volume, that are highly disturbed in Covid-19 and linked with poor clinical outcomes. Therefore, this present study aimed to find the potential association between AVP serum level and inflammatory disorders in Covid-19. It has been observed by different recent studies that physiological response due to fever, pain, hypovolemia, dehydration, and psychological stress is characterized by activation release of AVP to counter-balance high blood viscosity in Covid-19 patients. In addition, activated immune cells mainly T and B lymphocytes and released pro-inflammatory cytokines stimulate discharge of stored AVP from immune cells, which in a vicious cycle trigger release of pro-inflammatory cytokines. Vasopressin receptor antagonists have antiviral and anti-inflammatory effects that may inhibit AVP-induced hyponatremia and release of pro-inflammatory cytokines in Covid-19. In conclusion, release of AVP from hypothalamus is augmented in Covid-19 due to stress, high pro-inflammatory cytokines, high circulating AngII and inhibition of GABAergic neurons. In turn, high AVP level leads to induction of hyponatremia, inflammatory disorders, and development of complications in Covid-19 by activation of NF-κB and NLRP3 inflammasome with release of pro-inflammatory cytokines. Therefore, AVP antagonists might be novel potential therapeutic modality in treating Covid-19 through mitigation of AVP-mediated inflammatory disorders and hyponatremia.

摘要

在 COVID-19 中,由于细胞因子风暴的发展以及促炎细胞因子的大量释放和神经激素紊乱导致的血浆渗透压失调,系统性紊乱可能会进展。精氨酸加压素(AVP)参与调节身体渗透压系统、身体水分含量、血压和血浆容量,在 COVID-19 中这些都受到严重干扰,并与不良临床结局相关。因此,本研究旨在探讨 AVP 血清水平与 COVID-19 中炎症紊乱之间的潜在关联。不同的近期研究观察到,由于发热、疼痛、低血容量、脱水和心理应激引起的生理反应特征是激活 AVP 的释放,以对抗 COVID-19 患者的高血液粘度。此外,激活的免疫细胞主要是 T 和 B 淋巴细胞,并释放促炎细胞因子,刺激储存的 AVP 从免疫细胞中释放,这在一个恶性循环中触发促炎细胞因子的释放。血管加压素受体拮抗剂具有抗病毒和抗炎作用,可能抑制 COVID-19 中 AVP 诱导的低钠血症和促炎细胞因子的释放。总之,由于应激、高促炎细胞因子、循环中高 AngII 和 GABA 能神经元的抑制,下丘脑释放的 AVP 在 COVID-19 中增加。反过来,AVP 水平的升高通过激活 NF-κB 和 NLRP3 炎症小体并释放促炎细胞因子,导致 COVID-19 中低钠血症、炎症紊乱和并发症的发展。因此,AVP 拮抗剂可能是一种通过减轻 AVP 介导的炎症紊乱和低钠血症治疗 COVID-19 的新的潜在治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1306/8440235/9666a00b871e/ga1_lrg.jpg

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