TY - JOUR
T1 - Preactivated and disaggregated shape-changed platelets protected against acute respiratory distress syndrome complicated by sepsis through inflammation suppression
AU - Day, Yuan Ji
AU - Chen, Kuan Hung
AU - Chen, Yi Ling
AU - Huang, Tien Hung
AU - Sung, Pei Hsun
AU - Lee, Fan Yen
AU - Chen, Chih Hung
AU - Chai, Han Tan
AU - Yin, Tsung Cheng
AU - Chiang, Hsin Ju
AU - Chung, Sheng Ying
AU - Chang, Hsueh Wen
AU - Yip, Hon Kan
N1 - Publisher Copyright:
Copyright © 2016 by the Shock Society.
PY - 2016/10/1
Y1 - 2016/10/1
N2 - Background: This study tested the hypothesis that preactivated and disaggregated shape-changed platelet (PreD-SCP) therapy attenuates lung injury from acute respiratory distress syndrome (ARDS) induced by 100% oxygen inhalation and complicated by sepsis through peritoneal administration of 1.5 mg/kg lipopolysaccharide (LPS). Methods: Adult male Sprague-Dawley rats, weighing 325 to 350 g, were randomized into group 1 (normal controls [NC]), group 2 (NC + PreD-SCP [3.0 × 108, intravenous administration]), group 3 (ARDS-LPS), and group 4 (ARDS-LPS + PreDSCP), and sacrificed by 72 h after ARDS induction. Results: The lung injury score was significantly higher in group 3 than that in other groups, and significantly higher in group 4 than that in groups 1 and 2, whereas the numbers of alveolar sacs and oxygen saturation (%) showed a reversed pattern compared with that of lung injury score among the four groups (all P < 0.0001) without significant difference between groups 1 and 2. The expressions of proinflammatory cells (CD11+, CD14+, CD68+) and proteins (tumor necrosis factor [TNF]-α, nuclear factor [NF]-κB, interleukin [IL]-1ββ, matrix metalloproteinase [MMP]-9, inducible nitric oxide synthase, intercellular adhesion molecule-1) exhibited a pattern identical to the lung injury score. Circulating levels of white blood cell, IL-6, TNF-α, myeloperoxidase and CCL5, and pulmonary protein expressions of oxidative stress (NOX-1/NOX-2, oxidized protein), apoptotic (Bax, cleaved caspase 3/poly (ADP-ribose) polymerase), fibrotic (Smad3, transforming growth factor [TGF]-β), and DNA damage (γ-H2AX) biomarkers showed an identical pattern, whereas protein expressions of antifibrotic (Smad1/5, bone morphogenetic protein [BMP]-2) and antiinflammatory (Bcl-2) biomarkers demonstrated an opposite pattern comparedwith the proinflammatory indicesamong the four groups (all P < 0.001). Conclusions: PreD-SCP therapy effectively improved lung injury in ARDS complicated by sepsis.
AB - Background: This study tested the hypothesis that preactivated and disaggregated shape-changed platelet (PreD-SCP) therapy attenuates lung injury from acute respiratory distress syndrome (ARDS) induced by 100% oxygen inhalation and complicated by sepsis through peritoneal administration of 1.5 mg/kg lipopolysaccharide (LPS). Methods: Adult male Sprague-Dawley rats, weighing 325 to 350 g, were randomized into group 1 (normal controls [NC]), group 2 (NC + PreD-SCP [3.0 × 108, intravenous administration]), group 3 (ARDS-LPS), and group 4 (ARDS-LPS + PreDSCP), and sacrificed by 72 h after ARDS induction. Results: The lung injury score was significantly higher in group 3 than that in other groups, and significantly higher in group 4 than that in groups 1 and 2, whereas the numbers of alveolar sacs and oxygen saturation (%) showed a reversed pattern compared with that of lung injury score among the four groups (all P < 0.0001) without significant difference between groups 1 and 2. The expressions of proinflammatory cells (CD11+, CD14+, CD68+) and proteins (tumor necrosis factor [TNF]-α, nuclear factor [NF]-κB, interleukin [IL]-1ββ, matrix metalloproteinase [MMP]-9, inducible nitric oxide synthase, intercellular adhesion molecule-1) exhibited a pattern identical to the lung injury score. Circulating levels of white blood cell, IL-6, TNF-α, myeloperoxidase and CCL5, and pulmonary protein expressions of oxidative stress (NOX-1/NOX-2, oxidized protein), apoptotic (Bax, cleaved caspase 3/poly (ADP-ribose) polymerase), fibrotic (Smad3, transforming growth factor [TGF]-β), and DNA damage (γ-H2AX) biomarkers showed an identical pattern, whereas protein expressions of antifibrotic (Smad1/5, bone morphogenetic protein [BMP]-2) and antiinflammatory (Bcl-2) biomarkers demonstrated an opposite pattern comparedwith the proinflammatory indicesamong the four groups (all P < 0.001). Conclusions: PreD-SCP therapy effectively improved lung injury in ARDS complicated by sepsis.
KW - Acute lung injury
KW - Anti-inflammation
KW - Apoptosis
KW - Ischemia-reperfusion
KW - Oxidative stress
KW - Proinflammatory cytokines
UR - https://www.scopus.com/pages/publications/84964068060
U2 - 10.1097/SHK.0000000000000617
DO - 10.1097/SHK.0000000000000617
M3 - 文章
C2 - 27058048
AN - SCOPUS:84964068060
SN - 1073-2322
VL - 46
SP - 575
EP - 586
JO - Shock
JF - Shock
IS - 5
ER -
