Targeting of nicotinamide phosphoribosyltransferase enzymatic activity ameliorates lung damage induced by ischemia/reperfusion in rats

Respiratory Research

Research

Wen-I Liao¹  Shi-Jye Chu²  Min-Hui Li³  Shih-En Tang⁴  Shu-Yu Wu⁵  Kun-Lun Huang⁶  Hsin-Ping Pao⁷  Geng-Chin Wu⁸ 

[1] Department of Emergency Medicine, Tri-Service General Hospital, Taipei, Taiwan;Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Chenggong Road, Neihu 114, Taipei, Taiwan;Department of Physical Medicine and Rehabilitation, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan;Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan;The Graduate Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei, Taiwan;The Graduate Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei, Taiwan;Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan;The Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan;The Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan;Department of Internal Medicine, Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan;

关键词: Acute lung injury;    Ischemia-reperfusion;    Visfatin;    Nicotinamide phosphoribosyltransferase;    pre-B cell colony-enhancing factor;   

DOI  :  10.1186/s12931-017-0557-2

 received in 2016-09-06, accepted in 2017-04-18,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundEmerging evidence reveals that nicotinamide phosphoribosyltransferase (NAMPT) has a significant role in the pathophysiology of the inflammatory process. NAMPT inhibition has a beneficial effect in the treatment of a variety of inflammatory diseases. However, it remains unclear whether NAMPT inhibition has an impact on ischemia-reperfusion (I/R)-induced acute lung injury. In this study, we examined whether NAMPT inhibition provided protection against I/R lung injury in rats.MethodsIsolated perfused rat lungs were subjected to 40 min of ischemia followed by 60 min of reperfusion. The rats were randomly allotted to the control, control + FK866 (NAMPT inhibitor, 10 mg/kg), I/R, or I/R + FK866 groups (n = 6 per group). The effects of FK866 on human alveolar epithelial cells exposed to hypoxia-reoxygenation (H/R) were also investigated.ResultsTreatment with FK866 significantly attenuated the increases in lung edema, pulmonary arterial pressure, lung injury scores, and TNF-α, CINC-1, and IL-6 concentrations in bronchoalveolar lavage fluid in the I/R group. Malondialdehyde levels, carbonyl contents and MPO-positive cells in lung tissue were also significantly reduced by FK866. Additionally, FK866 mitigated I/R-stimulated degradation of IκB-α, nuclear translocation of NF-κB, Akt phosphorylation, activation of mitogen-activated protein kinase, and downregulated MKP-1 activity in the injured lung tissue. Furthermore, FK866 increased Bcl-2 and decreased caspase-3 activity in the I/R rat lungs. Comparably, the in vitro experiments showed that FK866 also inhibited IL-8 production and NF-κB activation in human alveolar epithelial cells exposed to H/R.ConclusionsOur findings suggest that NAMPT inhibition may be a novel therapeutic approach for I/R-induced lung injury. The protective effects involve the suppression of multiple signal pathways.

【 授权许可】

CC BY   
© The Author(s). 2017