PMID- 32826806
OWN - NLM
STAT- MEDLINE
DCOM- 20220113
LR  - 20220113
IS  - 1540-0514 (Electronic)
IS  - 1073-2322 (Linking)
VI  - 55
IP  - 5
DP  - 2021 May 1
TI  - Trauma-Hemorrhage Stimulates Immune Defense, Mitochondrial Dysfunction, 
      Autophagy, and Apoptosis in Pig Liver at 72 h.
PG  - 630-639
LID - 10.1097/SHK.0000000000001556 [doi]
AB  - Hepatic dysfunction frequently occurs after trauma-hemorrhage, resulting in 
      severe pathophysiological responses that include leukocyte shifting and 
      self-mediated mechanisms of cells, such as autophagy and apoptosis. This in vivo 
      study aimed to characterize mitochondrial morphology, leukocyte reaction, and the 
      processes of autophagy and apoptosis after polytrauma hemorrhage (TH) in a 
      long-term, large animal model.Liver tissue was taken from a porcine TH model 
      (hemorrhagic shock, blunt chest trauma, tibia fracture, and liver laceration) 
      with an intensive care unit follow-up of 72 h. The ultrastructural changes of the 
      liver tissue after TH were evaluated by transmission electron microscopy. The 
      leukocyte phenotypes and autophagy and apoptosis pathways were elucidated by 
      immunohistofluorescence, Western blot, and terminal deoxynucleotidyl transferase 
      dUTP nick-end labeling (TUNEL).In addition to post-traumatic changes in the 
      mitochondrial morphology, the biomarkers of anti-inflammatory macrophages (CD163) 
      and reparative monocytes (CD11R3 and CD16) were upregulated, while the inducible 
      nitric oxide synthase was downregulated after TH. Furthermore, the 
      autophagy-related protein expressions of LC3 and Beclin-1 were upregulated, 
      whereas the protein expression of P62 was downregulated after TH. Costaining 
      showed that the macrophages were LC3 (or Beclin-1) positive and that CD163 was 
      copositive and upregulated. Apoptosis biomarkers (cleaved-caspase-3/caspase-3 and 
      Bcl-2) increased after TH, which is in line with TUNEL results.In conclusion, the 
      observed findings indicate that mitochondrial dysfunction might be one trigger of 
      hepatic autophagy and apoptosis after TH. These processes occur together with the 
      activation of anti-inflammatory leukocytes in liver tissue. Further studies are 
      needed to elucidate the potential therapeutic effects of inhibiting mitochondrial 
      swelling during autophagy or apoptosis.
CI  - Copyright (c) 2020 by the Shock Society.
FAU - Shi, Yulong
AU  - Shi Y
AD  - Department of Trauma and Reconstructive Surgery, RWTH Aachen University Hospital, 
      Aachen, Germany.
FAU - Greven, Johannes
AU  - Greven J
AD  - Department of Trauma and Reconstructive Surgery, RWTH Aachen University Hospital, 
      Aachen, Germany.
FAU - Guo, Weijun
AU  - Guo W
AD  - Department of Trauma and Reconstructive Surgery, RWTH Aachen University Hospital, 
      Aachen, Germany.
FAU - Luo, Peng
AU  - Luo P
AD  - Department of Trauma and Reconstructive Surgery, RWTH Aachen University Hospital, 
      Aachen, Germany.
FAU - Xu, Ding
AU  - Xu D
AD  - Department of Trauma and Reconstructive Surgery, RWTH Aachen University Hospital, 
      Aachen, Germany.
FAU - Wang, Weikang
AU  - Wang W
AD  - Department of Trauma and Reconstructive Surgery, RWTH Aachen University Hospital, 
      Aachen, Germany.
FAU - Relja, Borna
AU  - Relja B
AD  - Head of Experimental Radiology, Department of Radiology and Nuclear Medicine, 
      University Hospital Magdeburg, Magdeburg, Germany.
FAU - Vollrath, Jan T
AU  - Vollrath JT
AD  - Department of Trauma, Hand and Reconstructive Surgery, University Hospital 
      Frankfurt, Goethe University, Frankfurt am Main, Germany.
FAU - Buhl, Eva Miriam
AU  - Buhl EM
AD  - Electron Microscopy Facility, Institute for Pathology, University Hospital RWTH 
      Aachen, Aachen, Germany.
FAU - Horst, Klemens
AU  - Horst K
AD  - Department of Trauma and Reconstructive Surgery, RWTH Aachen University Hospital, 
      Aachen, Germany.
FAU - Bolierakis, Eftychios
AU  - Bolierakis E
AD  - Department of Trauma and Reconstructive Surgery, RWTH Aachen University Hospital, 
      Aachen, Germany.
FAU - Blasius, Felix
AU  - Blasius F
AD  - Department of Trauma and Reconstructive Surgery, RWTH Aachen University Hospital, 
      Aachen, Germany.
FAU - Hildebrand, Frank
AU  - Hildebrand F
AD  - Department of Trauma and Reconstructive Surgery, RWTH Aachen University Hospital, 
      Aachen, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Shock
JT  - Shock (Augusta, Ga.)
JID - 9421564
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - *Autophagy
MH  - Hemorrhage/*complications/*immunology
MH  - Leukocytes/*immunology
MH  - Liver/*immunology/*pathology
MH  - Male
MH  - Mitochondrial Diseases/*etiology
MH  - Multiple Trauma/*complications/*immunology
MH  - Swine
COIS- The authors report no conflicts of interest.
EDAT- 2020/08/23 06:00
MHDA- 2022/01/14 06:00
CRDT- 2020/08/23 06:00
PHST- 2020/08/23 06:00 [pubmed]
PHST- 2022/01/14 06:00 [medline]
PHST- 2020/08/23 06:00 [entrez]
AID - 00024382-202105000-00009 [pii]
AID - 10.1097/SHK.0000000000001556 [doi]
PST - ppublish
SO  - Shock. 2021 May 1;55(5):630-639. doi: 10.1097/SHK.0000000000001556.