PMID- 32686659
OWN - NLM
STAT- MEDLINE
DCOM- 20210505
LR  - 20210505
IS  - 1643-3750 (Electronic)
IS  - 1234-1010 (Print)
IS  - 1234-1010 (Linking)
VI  - 26
DP  - 2020 Jul 20
TI  - Protective Effects of Ischemic Postconditioning on Livers in Rats with Limb 
      Ischemia-Reperfusion via Glycogen Synthase Kinase 3 beta (GSK-3beta)/Fyn/Nuclear 
      Receptor-Erythroid-2-Related Factor (Nrf2) Pathway.
PG  - e923049
LID - 10.12659/MSM.923049 [doi]
AB  - BACKGROUND Ischemia/reperfusion (I/R) injury not only exists in ischemic tissues 
      and organs, but also can cause damage to distant tissues and organs. As the 
      largest metabolic organ of the human body, the liver is very vulnerable to injury 
      after limb I/R. However, the mechanism of liver injury caused by limb I/R injury 
      has not been fully elucidated. This study investigated the effect and mechanism 
      of ischemic postconditioning (IPO) on the liver after hindlimb I/R in rats. 
      MATERIAL AND METHODS A rat model of hindlimb I/R was established and treated by 
      IPO. Liver function, changes of oxidative stress index and inflammation, Bcl-2 
      and Bax proteins, and apoptosis were assessed. The structural changes were 
      observed by electron microscopy. GSK-3ss/Fyn/Nrf2 levels were detected by 
      quantitative PCR and Western blot. RESULTS IPO significantly reduced serum AST, 
      ALP, LDH, and ALT levels induced by I/R. Compared with the I/R group, the levels 
      of SOD, GSH-Px, and CAT in the IPO group were significantly increased, while the 
      levels of MDA, MPO, and ROS were significantly decreased. The IPO group had 
      significantly higher Bcl-2 level and significantly lower Bax level compared to 
      the I/R group. Consistently, IPO decreased the apoptosis rate induced by I/R. 
      Furthermore, IPO lowered the levels of TNF-alpha, IL-1ss, IL-10, and INF-gamma and 
      alleviated the ultrastructural changes of hepatocytes. Finally, Nrf2, Fyn, and 
      GSK-3ss mRNA and protein levels in the IPO group were significantly higher than in 
      the I/R group. CONCLUSIONS IPO protects against liver injury caused by I/R injury 
      of the hindlimb, possibly via the GSK-3ss/Fyn/Nrf2 pathway.
FAU - Niu, Qibing
AU  - Niu Q
AD  - Department of Vascular Surgery, People's Hospital in Gansu Province, Gansu 
      University of Chinese Medicine, Lanzhou, Gansu, China (mainland).
FAU - Sun, Wanli
AU  - Sun W
AD  - Department of Vascular Surgery, People's Hospital in Gansu Province, Gansu 
      University of Chinese Medicine, Lanzhou, Gansu, China (mainland).
FAU - Chen, Quan
AU  - Chen Q
AD  - Department of Vascular Surgery, People's Hospital in Gansu Province, Gansu 
      University of Chinese Medicine, Lanzhou, Gansu, China (mainland).
FAU - Long, Yang
AU  - Long Y
AD  - Department of Vascular Surgery, People's Hospital in Gansu Province, Gansu 
      University of Chinese Medicine, Lanzhou, Gansu, China (mainland).
FAU - Cao, Wanjun
AU  - Cao W
AD  - Department of Vascular Surgery, People's Hospital in Gansu Province, Gansu 
      University of Chinese Medicine, Lanzhou, Gansu, China (mainland).
FAU - Wen, Shiqi
AU  - Wen S
AD  - Department of Vascular Surgery, People's Hospital in Gansu Province, Gansu 
      University of Chinese Medicine, Lanzhou, Gansu, China (mainland).
FAU - Li, Anqiang
AU  - Li A
AD  - Department of Vascular Surgery, People's Hospital in Gansu Province, Gansu 
      University of Chinese Medicine, Lanzhou, Gansu, China (mainland).
FAU - Dong, Fang
AU  - Dong F
AD  - Department of Vascular Surgery, People's Hospital in Gansu Province, Gansu 
      University of Chinese Medicine, Lanzhou, Gansu, China (mainland).
FAU - Shi, Hao
AU  - Shi H
AD  - Department of Vascular Surgery, People's Hospital in Gansu Province, Gansu 
      University of Chinese Medicine, Lanzhou, Gansu, China (mainland).
LA  - eng
PT  - Journal Article
DEP - 20200720
PL  - United States
TA  - Med Sci Monit
JT  - Medical science monitor : international medical journal of experimental and 
      clinical research
JID - 9609063
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Nfe2l2 protein, rat)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (bcl-2-Associated X Protein)
RN  - EC 2.7.10.2 (Proto-Oncogene Proteins c-fyn)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Glycogen Synthase Kinase 3 beta/metabolism
MH  - Hepatocytes/metabolism
MH  - Ischemia/metabolism
MH  - Ischemic Postconditioning/*methods
MH  - Liver/*blood supply/metabolism/pathology
MH  - Male
MH  - NF-E2-Related Factor 2/metabolism
MH  - Oxidative Stress
MH  - Proto-Oncogene Proteins c-fyn/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reperfusion/methods
MH  - Reperfusion Injury/metabolism/pathology/*therapy
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - bcl-2-Associated X Protein/metabolism
PMC - PMC7392060
COIS- Conflict of interest None.
EDAT- 2020/07/21 06:00
MHDA- 2021/05/06 06:00
PMCR- 2020/07/20
CRDT- 2020/07/21 06:00
PHST- 2020/07/21 06:00 [entrez]
PHST- 2020/07/21 06:00 [pubmed]
PHST- 2021/05/06 06:00 [medline]
PHST- 2020/07/20 00:00 [pmc-release]
AID - 923049 [pii]
AID - 10.12659/MSM.923049 [doi]
PST - epublish
SO  - Med Sci Monit. 2020 Jul 20;26:e923049. doi: 10.12659/MSM.923049.