PDF(Pubmed)
Abstract：
BACKGROUND: Coronaviral infection-induced acute lung injury has become a major threat to public health, especially through the ongoing pandemic of COVID-19. Apta-1 is a newly discovered Aptamer that has anti-inflammatory effects on systemic septic responses. The therapeutic effects of Apta-1 on coronaviral infection-induced acute lung injury and systemic responses were evaluated in the present study.
METHODS: Female A/J mice (at 12-14 weeks of age) were challenged with murine hepatitis virus 1 (MHV-1), a coronavirus, at 5000 PFU intranasally, followed by Apta-1 intravenously administered (100 mg/kg, twice) 1.5 h or 2 days after viral delivery. Animals were sacrificed at Day 2 or Day 4. Lung tissues were examined with H&E, immunohistochemistry staining, and western blotting. RT-qPCR was used for cytokine gene expression. Serum and plasma were collected for laboratory assessments.
RESULTS: Apta-1 treatment reduced viral titers, prevented MHV-1-induced reduction of circulating blood volume and hemolysis, reduced alveolar space hemorrhage, and protease-activated receptor 1 (PAR-1) cleavage. Apta-1 treatment also significantly reduced chemokine (MKC, MCP-1, and RANTES) levels, as well as AST, ALT, total bilirubin, and reduced unconjugated bilirubin levels in the serum.
CONCLUSIONS: Apta-1 showed therapeutic benefits in coronaviral infection-induced hemorrhage and PAR-1 cleavage in the lung. It also has anti-inflammatory effects systemically.
METHODS: Female A/J mice (at 12-14 weeks of age) were challenged with murine hepatitis virus 1 (MHV-1), a coronavirus, at 5000 PFU intranasally, followed by Apta-1 intravenously administered (100 mg/kg, twice) 1.5 h or 2 days after viral delivery. Animals were sacrificed at Day 2 or Day 4. Lung tissues were examined with H&E, immunohistochemistry staining, and western blotting. RT-qPCR was used for cytokine gene expression. Serum and plasma were collected for laboratory assessments.
RESULTS: Apta-1 treatment reduced viral titers, prevented MHV-1-induced reduction of circulating blood volume and hemolysis, reduced alveolar space hemorrhage, and protease-activated receptor 1 (PAR-1) cleavage. Apta-1 treatment also significantly reduced chemokine (MKC, MCP-1, and RANTES) levels, as well as AST, ALT, total bilirubin, and reduced unconjugated bilirubin levels in the serum.
CONCLUSIONS: Apta-1 showed therapeutic benefits in coronaviral infection-induced hemorrhage and PAR-1 cleavage in the lung. It also has anti-inflammatory effects systemically.
摘要：
背景：冠状病毒感染引起的急性肺损伤已成为公共卫生的主要威胁，特别是通过持续的COVID-19大流行。Apta-1是一种新发现的适体，对全身性败血症反应具有抗炎作用。本研究评估了Apta-1对冠状病毒感染引起的急性肺损伤和全身反应的治疗作用。
方法：用小鼠肝炎病毒1（MHV-1）攻击雌性A/J小鼠（12-14周龄），冠状病毒,在5000PFU鼻内，然后静脉内施用Apta-1（100mg/kg，两次）病毒递送后1.5小时或2天。在第2天或第4天处死动物。肺组织用H&E检查，免疫组织化学染色，和西方印迹。RT-qPCR用于细胞因子基因表达。收集血清和血浆用于实验室评估。
结果：Apta-1治疗降低了病毒滴度，防止MHV-1引起的循环血容量减少和溶血，减少肺泡间隙出血，和蛋白酶激活受体1(PAR-1)切割。Apta-1治疗也显著降低趋化因子(MKC，MCP-1和RANTES)水平，以及AST,ALT,总胆红素,和降低血清中未结合的胆红素水平。
结论：Apta-1对冠状病毒感染引起的肺出血和PAR-1裂解具有治疗作用。它还具有全身抗炎作用。
方法：用小鼠肝炎病毒1（MHV-1）攻击雌性A/J小鼠（12-14周龄），冠状病毒,在5000PFU鼻内，然后静脉内施用Apta-1（100mg/kg，两次）病毒递送后1.5小时或2天。在第2天或第4天处死动物。肺组织用H&E检查，免疫组织化学染色，和西方印迹。RT-qPCR用于细胞因子基因表达。收集血清和血浆用于实验室评估。
结果：Apta-1治疗降低了病毒滴度，防止MHV-1引起的循环血容量减少和溶血，减少肺泡间隙出血，和蛋白酶激活受体1(PAR-1)切割。Apta-1治疗也显著降低趋化因子(MKC，MCP-1和RANTES)水平，以及AST,ALT,总胆红素,和降低血清中未结合的胆红素水平。
结论：Apta-1对冠状病毒感染引起的肺出血和PAR-1裂解具有治疗作用。它还具有全身抗炎作用。
