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具有抗炎、抗血栓形成、抗氧化和抗纤维化特性的非特异性磷酸二酯酶抑制剂己酮可可碱在治疗 SARS-CoV-2 中的潜在用途。

Potential usefulness of pentoxifylline, a non-specific phosphodiesterase inhibitor with anti-inflammatory, anti-thrombotic, antioxidant, and anti-fibrogenic properties, in the treatment of SARS-CoV-2.

机构信息

Coronary Care Unit, National Institute of Cardiology in Mexico City, Mexico City, Mexico.

出版信息

Eur Rev Med Pharmacol Sci. 2020 Jul;24(13):7494-7496. doi: 10.26355/eurrev_202007_21921.

Abstract

Although most patients with coronavirus disease 2019 (COVID-19) have a good prognosis, in some cases, the disease progresses rapidly, and the mortality rate is high. Some evidence suggests that infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) produces a 'cytokine storm', which is related to acute respiratory distress syndrome or multi-organ dysfunction leading to physiological deterioration and death. It is important to highlight the state of hypercoagulability that can be triggered, involving microvascular thrombosis and vascular occlusive events, which are relevant to such poor outcomes. At present, no specific antiviral drug or vaccine is available for SARS-CoV-2 infection, and current research is aimed at preventing and mitigating damage to the target organs, mainly the lungs. In seeking therapies for patients with COVID-19, immunomodulators, cytokine antagonists and early anti-coagulation therapies have been tested in attempts to reduce the mortality rate. Pentoxifylline, a non-specific phosphodiesterase inhibitor widely used to improve the rheological properties of blood, has beneficial anti-inflammatory properties and can significantly reduce the serum levels of pro-inflammatory cytokines such as interleukin (IL)-6, IL-1, tumour necrosis factor-alpha, C-reactive protein and other immunoregulators. It has also been found to exert anti-thrombotic, antioxidant and anti-fibrogenic actions. These properties could help to prevent or mitigate the inflammatory response and hypercoagulability that develop with SARS-CoV-2 infection, decreasing multi-organ dysfunction manifesting primarily as acute lung injury.

摘要

虽然大多数 2019 冠状病毒病(COVID-19)患者预后良好,但在某些情况下,疾病进展迅速,死亡率高。有证据表明,严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)感染会产生“细胞因子风暴”,这与急性呼吸窘迫综合征或多器官功能障碍有关,导致生理恶化和死亡。值得强调的是,可能会引发的高凝状态,涉及微血管血栓形成和血管闭塞事件,这与预后不良有关。目前,尚无针对 SARS-CoV-2 感染的特异性抗病毒药物或疫苗,目前的研究旨在预防和减轻靶器官(主要是肺部)的损伤。在为 COVID-19 患者寻求治疗方法时,免疫调节剂、细胞因子拮抗剂和早期抗凝治疗已被尝试用于降低死亡率。己酮可可碱是一种广泛用于改善血液流变学特性的非特异性磷酸二酯酶抑制剂,具有有益的抗炎特性,可显著降低白细胞介素(IL)-6、IL-1、肿瘤坏死因子-α、C 反应蛋白和其他免疫调节剂等促炎细胞因子的血清水平。它还具有抗血栓形成、抗氧化和抗纤维化作用。这些特性可能有助于预防或减轻 SARS-CoV-2 感染引起的炎症反应和高凝状态,减少主要表现为急性肺损伤的多器官功能障碍。

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