Programa de Pós-graduação em Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627 - Pampulha, Belo Horizonte, MG, 31270-901, Brazil.
Hospital das Clínicas da Universidade Federal de Minas Gerais/Ebserh, Belo Horizonte, Minas Gerais, Brazil.
Inflamm Res. 2024 Nov;73(11):2009-2022. doi: 10.1007/s00011-024-01948-8. Epub 2024 Sep 18.
Pro-resolving molecules, including the peptide Angiotensin-(1-7) [Ang-(1-7)], have potential adjunctive therapy for infections. Here we evaluate the actions of Ang-(1-7) in betacoronavirus infection in mice.
C57BL/6J mice were infected intranasally with the murine betacoronavirus MHV-3 and K18-hACE2 mice were infected with SARS-CoV-2. Mice were treated with Ang-(1-7) (30 µg/mouse, i.p.) at 24-, 36-, and 48-hours post-infection (hpi) or at 24, 36, 48, 72, and 96 h. For lethality evaluation, one additional dose of Ang-(1-7) was given at 120 hpi. At 3- and 5-days post- infection (dpi) blood cells, inflammatory mediators, viral loads, and lung histopathology were evaluated.
Ang-(1-7) rescued lymphopenia in MHV-infected mice, and decreased airways leukocyte infiltration and lung damage at 3- and 5-dpi. The levels of pro-inflammatory cytokines and virus titers in lung and plasma were decreased by Ang-(1-7) during MHV infection. Ang-(1-7) improved lung function and increased survival rates in MHV-infected mice. Notably, Ang-(1-7) treatment during SARS-CoV-2 infection restored blood lymphocytes to baseline, decreased weight loss, virus titters and levels of inflammatory cytokines, resulting in improvement of pulmonary damage, clinical scores and lethality rates.
Ang-(1-7) protected mice from lung damage and death during betacoronavirus infections by modulating inflammation, hematological parameters and enhancing viral clearance.
包括肽血管紧张素转化酶 2（Angiotensin-(1-7)）在内的促解决分子在感染中具有潜在的辅助治疗作用。在这里，我们评估 Ang-(1-7) 在小鼠β冠状病毒感染中的作用。
C57BL/6J 小鼠经鼻腔感染鼠β冠状病毒 MHV-3，K18-hACE2 小鼠感染 SARS-CoV-2。感染后 24、36 和 48 小时（hpi）或 24、36、48、72 和 96 小时（hpi），用 Ang-(1-7)（30μg/只，腹腔内注射）治疗小鼠。对于致死性评估，在 120 hpi 时给予额外剂量的 Ang-(1-7)。在感染后 3 和 5 天（dpi）评估血液细胞、炎症介质、病毒载量和肺组织病理学。
Ang-(1-7) 挽救了 MHV 感染小鼠的淋巴细胞减少症，并在 3 和 5 dpi 时减少了气道白细胞浸润和肺损伤。在 MHV 感染期间，Ang-(1-7) 降低了肺和血浆中促炎细胞因子和病毒滴度。Ang-(1-7) 改善了 MHV 感染小鼠的肺功能并提高了存活率。值得注意的是，在 SARS-CoV-2 感染期间给予 Ang-(1-7) 治疗可将淋巴细胞恢复到基线水平，减少体重减轻、病毒滴度和炎症细胞因子水平，从而改善肺部损伤、临床评分和死亡率。
Ang-(1-7) 通过调节炎症、血液学参数和增强病毒清除作用，保护小鼠免受β冠状病毒感染引起的肺损伤和死亡。
