烟酰胺磷酸核糖转移酶抑制剂FK866通过抑制炎症反应减轻LPS诱导的新生小鼠急性肺损伤OA

Objective This study investigates whether the nicotinamide phosphoribosyltransferase(NAMPT)inhibitor FK866 can mitigate systemic inflammatory responses and lung injury using a lipopolysaccharide(LPS)-induced acute lung injury(ALI model in neonatal mice.Methods Neonatal C57BL/6J male mice were randomly divided into four groups using a random number table method:control group,FK866 group,LPS group,and FK866+LPS group.The control group received intraperitoneal injections of equivalent saline on days 5-7.The FK866 and FK866+LPS groups were pretreated with 10 mg/(kg·d)FK866 via intraperitoneal injection for two consecutive days starting on day 5.The LPS and FK866+LPS groups received 10 mg/kg LPS intraperitoneally on day 7 to induce systemic inflammation and ALI.All neonatal mice were sacrificed on day 8 for collection of lung tissues and serum.Results Hematoxylin-eosin(HE)staining revealed significantly higher lung injury scores in the LPS group compared to the control group(P<0.05).The FK866+LPS group showed significantly lower lung injury scores than the LPS group(P<0.05).Serum levels of inflammatory factors including tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,and IL-6 were significantly elevated in the LPS group compared to controls(P<0.05),while these inflammatory markers were significantly reduced in the FK866+LPS group compared to the LPS group(P<0.05).Conclusion FK866 alleviates systemic inflammation and inflammatory-associated ALI in a neonatal mouse model of sepsis-related ALI,suggesting that NAMPT inhibitors may play a protective role in mitigating neonatal acute lung injury.