Yuan Du, Collage Richard D, Huang Hai, Zhang Xianghong, Kautza Benjamin C, Lewis Anthony J, Zuckerbraun Brian S, Tsung Allan, Angus Derek C, Rosengart Matthew R
Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213; The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China;
Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213;
Proc Natl Acad Sci U S A. 2016 May 10;113(19):5239-44. doi: 10.1073/pnas.1515296113. Epub 2016 Apr 25.
Evidence suggests that light and circadian rhythms profoundly influence the physiologic capacity with which an organism responds to stress. However, the ramifications of light spectrum on the course of critical illness remain to be determined. Here, we show that acute exposure to bright blue spectrum light reduces organ injury by comparison with bright red spectrum or ambient white fluorescent light in two murine models of sterile insult: warm liver ischemia/reperfusion (I/R) and unilateral renal I/R. Exposure to bright blue light before I/R reduced hepatocellular injury and necrosis and reduced acute kidney injury and necrosis. In both models, blue light reduced neutrophil influx, as evidenced by reduced myeloperoxidase (MPO) within each organ, and reduced the release of high-mobility group box 1 (HMGB1), a neutrophil chemotactant and key mediator in the pathogenesis of I/R injury. The protective mechanism appeared to involve an optic pathway and was mediated, in part, by a sympathetic (β3 adrenergic) pathway that functioned independent of significant alterations in melatonin or corticosterone concentrations to regulate neutrophil recruitment. These data suggest that modifying the spectrum of light may offer therapeutic utility in sterile forms of cellular injury.
有证据表明,光线和昼夜节律会深刻影响生物体应对压力的生理能力。然而,光谱对危重病病程的影响仍有待确定。在此,我们表明,在两种无菌损伤的小鼠模型中,与亮红色光谱或环境白色荧光相比,急性暴露于亮蓝色光谱可减轻器官损伤:温性肝缺血/再灌注(I/R)和单侧肾I/R。在I/R之前暴露于亮蓝光可减轻肝细胞损伤和坏死,并减轻急性肾损伤和坏死。在这两种模型中,蓝光减少了中性粒细胞的流入,每个器官内髓过氧化物酶(MPO)减少证明了这一点,并且减少了高迁移率族蛋白B1(HMGB1)的释放,HMGB1是一种中性粒细胞趋化剂,也是I/R损伤发病机制中的关键介质。保护机制似乎涉及一条视觉通路,部分由交感神经(β3肾上腺素能)通路介导,该通路的作用独立于褪黑素或皮质酮浓度的显著变化,以调节中性粒细胞募集。这些数据表明,改变光谱可能在无菌形式的细胞损伤中具有治疗作用。