Department of Pathophysiology, College of Veterinary Medicine, China Agricultural University, Beijing, China; Institute of Molecular Ecology and Evolution, Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai, China.
Influenza Other Respir Viruses. 2013 Nov;7(6):945-53. doi: 10.1111/irv.12067. Epub 2013 Jan 22.
Acute lung injury is an important cause of death in humans infected with H5N1. It has been found that oxygen free radicals (OFRs) are elevated in lung tissue during influenza virus infections. In this study, we used a mouse model to explore the role of OFRs in acute lung injury caused by H5N1 viral infection.
Four- to six-week-old male specific pathogen-free BALB/c mice were inoculated intranasally with 10(5) 50% tissue culture infective doses (TCID50) of highly pathogenic A/Chicken/Hebei/108/2002 (H5N1) viruses and were then given 1000 IU of lauric acid modified superoxide dismutase (LA-SOD) by intraperitoneal injection, starting 2 days post-infection and continuing for 6 days.
The extent of lung injury and the concentration of OFRs were higher, and the SOD activity was lower in H5N1 virus-infected mice than that in uninfected control mice on days 3, 6, and 7 post-inoculation. Weak amelioration of clinical signs, a minor decrease in the total mortality and the extent of lung injury, and the lower OFRs concentration were seen in the LA-SOD treatment group, but a reduction in lung virus titers was not observed in the LA-SOD treatment at all time points.
The LA-SOD treatment has a mild inhibitory effect on H5N1 influenza virus infection in mice. OFRs, therefore, might play an important role in the pathogenesis of acute lung injury induced by H5N1 virus.
急性肺损伤是人类感染 H5N1 后的一个重要死亡原因。研究发现,流感病毒感染时肺组织中氧自由基(OFRs)升高。本研究采用小鼠模型探讨 OFRs 在 H5N1 病毒感染引起的急性肺损伤中的作用。
4-6 周龄雄性无特定病原体 BALB/c 小鼠经鼻腔接种 10(5)50%组织培养感染剂量(TCID50)的高致病性 A/鸡/河北/108/2002(H5N1)病毒,然后腹腔注射 1000 IU 月桂酸修饰超氧化物歧化酶(LA-SOD),感染后第 2 天开始,连续 6 天。
与未感染对照小鼠相比,H5N1 病毒感染小鼠在感染后第 3、6 和 7 天肺损伤程度更高,OFRs 浓度更高,SOD 活性更低。LA-SOD 治疗组临床症状改善不明显,总死亡率和肺损伤程度略有降低,OFRs 浓度降低,但 LA-SOD 治疗组在所有时间点均未观察到肺病毒滴度降低。
LA-SOD 治疗对小鼠 H5N1 流感病毒感染有轻度抑制作用。因此,OFRs 可能在 H5N1 病毒引起的急性肺损伤发病机制中起重要作用。