Zhuang Shihao, Tang Qiuyu, Chen Ping, Wang Chengyi, Liu Guanghua
Department of Pediatrics, Fujian Children's Hospital, Fuzhou, Fujian China, 350000.
Department of Pediatrics, Fujian Maternity and Child Health Hospital Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China 350000.
Acta Pharm. 2022 Apr 13;72(3):415-425. doi: 10.2478/acph-2022-0022. Print 2022 Sep 1.
Respiratory syncytial virus (RSV) is the most common cause of small airways inflammation in the lungs (bronchiolitis) in neonates and immunocompromised adults. The deregulation of cellular and plasma components leads to increased morbidity and mortality. The activation of the clotting cascade plays a key role in the progression of disease severity during viral infection. The current investigation studied the effect of bivalirudin (BR) on the progression and cellular effects of RSV-induced infection in the neonatal mice model. Mice (5-7 days old) were inoculated intranasally with RSV with or without BR administration (2 mg kg day, ) for 2 weeks. Tissue histopathology, inflammatory signalling genes such as TLR, and cytokines were analyzed. The results showed pneumocytes exhibiting nuclear pyknosis, cellular infiltration in lung tissue and increased lung titers in RSV-infected mice compared to the control. Furthermore, RSV-infected mice demonstrated altered clotting parameters such as D-dimer, soluble thrombomodulin, and increased inflammatory cytokines IL-5, 6, IFN-γ, IL-13, and CXCL1. Additionally, the mRNA expression analysis displayed increased levels of IL-33, TLR3, and TLR7 genes in RSV-infected lung tissue. Further, to delineate the role of micro RNAs, the qRT-PCR analysis was done, and the results displayed an increase in miR-136, miR-30b, and let-7i. At the same time, the down-regulated expression of miR-221 in RSV-infected mice compared to the control. BR treatment reduced the cellular infiltration with reduced inflammatory cytokines and normalized clotting indices. Thus, the study shows that RSV infection induces specific changes in lung tissue and the clotting related signalling mechanism. Additionally, BR treatment significantly reduces bronchiolitis and prevents the severity of the infections suggesting that BR can possibly be used to reduce the viral-mediated infections in neonates.
呼吸道合胞病毒（RSV）是新生儿和免疫功能低下成人肺部小气道炎症（细支气管炎）最常见的病因。细胞和血浆成分失调会导致发病率和死亡率增加。凝血级联反应的激活在病毒感染期间疾病严重程度的进展中起关键作用。本研究调查了比伐卢定（BR）对新生小鼠模型中RSV诱导感染的进展和细胞效应的影响。将5 - 7日龄的小鼠经鼻接种RSV，同时或不给予BR（2毫克/千克/天），持续2周。分析了组织组织病理学、炎症信号基因如Toll样受体（TLR）和细胞因子。结果显示，与对照组相比，RSV感染小鼠的肺细胞出现核固缩、肺组织细胞浸润且肺滴度增加。此外，RSV感染小鼠的凝血参数如D - 二聚体、可溶性血栓调节蛋白发生改变，炎症细胞因子白细胞介素 - 5、6、干扰素 - γ、白细胞介素 - 13和CXC趋化因子配体1增加。此外，mRNA表达分析显示RSV感染的肺组织中白细胞介素 - 33、TLR3和TLR7基因水平升高。进一步，为了阐明微小RNA的作用，进行了定量逆转录 - 聚合酶链反应（qRT - PCR）分析，结果显示微小RNA - 136、微小RNA - 30b和微小RNA - let - 7i增加。同时，与对照组相比，RSV感染小鼠中微小RNA - 221表达下调。BR治疗减少了细胞浸润，降低了炎症细胞因子水平并使凝血指标恢复正常。因此，该研究表明RSV感染会引起肺组织和凝血相关信号机制的特定变化。此外，BR治疗显著减轻细支气管炎并预防感染的严重程度，这表明BR可能可用于减少新生儿的病毒介导感染。
