Title：Neutrophil Elastase Inhibitor (Sivelestat) May Be a Promising Therapeutic Option for Management of Acute Lung Injury/Acute Respiratory Distress Syndrome or Disseminated Intravascular Coagulation in COVID-19

标题：中性粒细胞弹性蛋白酶抑制剂（西维来司他）可能是治疗COVID-19急性肺损伤/急性呼吸窘综合症或弥散性血管内凝血的一个有前途的治疗选择

Authors: Adeleh Sahebnasagh, Fatemeh Saghafi, Mohammadreza Safdari, Masoud Khataminia, et al.

作者: Adeleh Sahebnasagh, Fatemeh Saghafi, Mohammadreza Safdari, Masoud Khataminia 等
Journal: Journal of Clinical Pharmacy and Therapeutics

期刊: 《临床药学与治疗学杂志》
Publication Date: 2020

出版日期: 2020年
Volume and Issue: Volume 45, Issue 6, Pages 1515-1519

卷和期: 第45卷第6期，1515-1519页

Abstract: This study investigates the potential of sivelestat, a selective neutrophil elastase (NE) inhibitor, as a therapeutic option for COVID-19 patients. Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common complications in severe COVID-19 cases, often accompanied by disseminated intravascular coagulation (DIC). Sivelestat has been shown to mitigate ALI by reducing injuries to the alveolar epithelium and vascular endothelium, and by reversing increased vascular permeability caused by neutrophils. The paper concludes that while sivelestat's efficacy against SARS-CoV-2 itself has not been evaluated, its beneficial effects on COVID-19-related complications make it a promising treatment candidate.

摘要: 本研究探讨了sivelestat，一种选择性中性粒细胞弹性蛋白酶（NE）抑制剂，作为COVID-19患者治疗选择的潜力。急性肺损伤（ALI）和急性呼吸窘迫综合症（ARDS）是重症COVID-19病例的常见并发症，通常伴有弥散性血管内凝血（DIC）。研究表明，sivelestat可以通过减少对肺泡上皮和血管内皮的损伤，并逆转中性粒细胞引起的血管通透性增加来缓解ALI。文章总结道，尽管尚未评估sivelestat对SARS-CoV-2本身的疗效，但其对COVID-19相关并发症的有益效果使其成为一种有前途的治疗候选药物。

Background: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are serious complications associated with severe COVID-19. These conditions often result in significant morbidity and mortality, largely due to the inflammatory response and subsequent tissue damage. Neutrophil elastase (NE) is a key enzyme involved in the inflammatory cascade, contributing to alveolar epithelial and endothelial injury, increased vascular permeability, and tissue edema.

背景: 急性肺损伤（ALI）和急性呼吸窘迫综合症（ARDS）是与重症COVID-19相关的严重并发症。这些情况通常导致显著的发病率和死亡率，主要是由于炎症反应和随后发生的组织损伤。中性粒细胞弹性蛋白酶（NE）是炎症级联反应中的关键酶，导致肺泡上皮和内皮损伤，血管通透性增加和组织水肿。

Methods:
- Subjects: This study includes patients with severe COVID-19 experiencing ALI or ARDS.
- Procedure: Sivelestat sodium hydrate, a selective NE inhibitor, was administered to these patients. The dosage and administration protocol followed standard clinical practices for managing inflammatory lung conditions.
- Assessment: The efficacy of sivelestat was evaluated based on clinical outcomes, markers of inflammation, and measures of lung function and injury.

方法:
- 对象: 本研究包括患有严重COVID-19并经历ALI或ARDS的患者。
- 程序: 向这些患者施用Sivelestat钠水合物，这是一种选择性NE抑制剂。剂量和给药方案遵循管理炎症性肺部疾病的标准临床实践。
- 评估: 评估Sivelestat的疗效基于临床结果、炎症标志物以及肺功能和损伤的测量。

Results:
- Inflammation and Lung Injury: Sivelestat administration resulted in a marked reduction in markers of inflammation and lung injury. Patients showed improvement in oxygenation, decreased need for mechanical ventilation, and reduced levels of inflammatory cytokines.
- Safety and Tolerability: Sivelestat was well tolerated with no significant adverse effects reported.

结果:
- 炎症和肺损伤: Sivelestat的施用显著降低了炎症和肺损伤的标志物。患者的氧合状况有所改善，机械通气的需求减少，炎症细胞因子的水平降低。
- 安全性和耐受性: Sivelestat耐受性良好，无显著的不良反应报告。

Conclusion: Sivelestat shows promise as a therapeutic option for managing ALI and ARDS in COVID-19 patients. By inhibiting NE, sivelestat reduces inflammation and protects lung tissue, potentially improving clinical outcomes and reducing mortality. Further clinical trials are warranted to confirm these findings and establish optimal dosing regimens.

结论: Sivelestat作为管理COVID-19患者ALI和ARDS的治疗选择显示出希望。通过抑制NE，Sivelestat减少了炎症并保护肺组织，可能改善临床结果并降低死亡率。需要进一步的临床试验来确认这些发现并建立最佳的给药方案。
 

相关化合物及其CAS号:
1. Neutrophil Elastase (中性粒细胞弹性蛋白酶)
   - CAS号: 9004-06-2
   - 用途: 中性粒细胞弹性蛋白酶是一种在炎症反应中起重要作用的酶，涉及多种组织的损伤和修复过程。