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急性肺损伤:Rho 激酶抑制剂的治疗作用。

Acute lung injury: The therapeutic role of Rho kinase inhibitors.

机构信息

Pharmaceutical Research Center, Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences, Mashhad, Iran.

University of South Florida, Tampa, FL, USA; Michigan State University, East Lansing, MI, USA.

出版信息

Pharmacol Res. 2020 May;155:104736. doi: 10.1016/j.phrs.2020.104736. Epub 2020 Mar 2.

Abstract

Acute lung injury (ALI) is a pulmonary illness with high rates of mortality and morbidity. Rho GTPase and its downstream effector, Rho kinase (ROCK), have been demonstrated to be involved in cell adhesion, motility, and contraction which can play a role in ALI. The electronic databases of Google Scholar, Scopus, PubMed, and Web of Science were searched to obtain relevant studies regarding the role of the Rho/ROCK signaling pathway in the pathophysiology of ALI and the effects of specific Rho kinase inhibitors in prevention and treatment of ALI. Upregulation of the RhoA/ROCK signaling pathway causes an increase of inflammation, immune cell migration, apoptosis, coagulation, contraction, and cell adhesion in pulmonary endothelial cells. These effects are involved in endothelium barrier dysfunction and edema, hallmarks of ALI. These effects were significantly reversed by Rho kinase inhibitors. Rho kinase inhibition offers a promising approach in ALI [ARDS] treatment.

摘要

急性肺损伤(ALI)是一种具有高死亡率和发病率的肺部疾病。Rho GTPase 及其下游效应物 Rho 激酶(ROCK)已被证明参与细胞黏附、运动和收缩,这在 ALI 中可能发挥作用。检索 Google Scholar、Scopus、PubMed 和 Web of Science 电子数据库,以获得关于 Rho/ROCK 信号通路在 ALI 病理生理学中的作用以及特定 Rho 激酶抑制剂在预防和治疗 ALI 中的作用的相关研究。RhoA/ROCK 信号通路的上调导致肺内皮细胞中的炎症、免疫细胞迁移、细胞凋亡、凝血、收缩和细胞黏附增加。这些作用涉及内皮细胞屏障功能障碍和水肿,这是 ALI 的标志。这些作用被 Rho 激酶抑制剂显著逆转。Rho 激酶抑制为 ALI [ARDS]的治疗提供了一种很有前途的方法。

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