PMID- 35527005
OWN - NLM
STAT- MEDLINE
DCOM- 20220510
LR  - 20220510
IS  - 1880-3989 (Electronic)
IS  - 0388-1350 (Linking)
VI  - 47
IP  - 5
DP  - 2022
TI  - Dexmedetomidine attenuates acute stress-induced liver injury in rats by 
      regulating the miR-34a-5p/ROS/JNK/p38 signaling pathway.
PG  - 169-181
LID - 10.2131/jts.47.169 [doi]
AB  - Dexmedetomidine (DEX) protects against acute stress-induced liver injury, but 
      what's less clear lies in the specific mechanism. To elucidate the specific 
      mechanism underlying DEX on acute stress-induced liver injury, an in vivo model 
      was constructed on rats with acute stress-induced liver injury by 15 min of 
      exhaustive swimming and 3 hr of immobilization. DEX (30 mug/kg) or miR-34a-5p 
      agomir was injected into model rats. Open field test was used to verify the 
      establishment of the model. Liver injury was observed by hematoxylin-eosin (H&E) 
      staining. Contents of norepinephrine (NE), alanine aminotransfease (ALT) and 
      aspartate aminotransferase (AST) in serum of rats were detected by enzyme-linked 
      immunosorbent assay (ELISA) and those of oxidative stress markers (reactive 
      oxygen species (ROS), Malondialdehyde (MDA), Glutathione (GSH), Superoxide 
      Dismutase (SOD) and Glutathione Peroxidase (GPX)) were measured using commercial 
      kits. Apoptosis of hepatocytes was detected by Terminal deoxynucleotidyl 
      transferase dUTP nick-end labeling (TUNEL) assay. Western blot was performed to 
      detect the expressions of SOD2, COX-2, cytochrome C, Cleaved caspase 3, Bax, 
      Bcl-2, P-JNK, JNK, P-p38, p38 and c-AMP, p-PKA and PKA in liver tissues. As a 
      result, liver injury in model rat was alleviated by DEX. DEX attenuated the 
      increase in the levels of NE, ALT, AST, MDA, ROS, apoptosis, SOD2, COX-2, 
      Cytochrome C, cleaved caspase 3, Bax, and P-JNK, P-p38, c-AMP, P-PKA and 
      miR-34a-5p, and the decrease in the levels of SOD, GPX, GSH and Bcl-2 in model 
      rats. Furthermore, miR-34a-5p overexpression could partly reverse the effects of 
      DEX. Collectively, DEX could alleviate acute stress-induced liver injury through 
      ROS/JNK/p38 signaling pathway via downregulation of miR-34a-5p.
FAU - Li, Dan
AU  - Li D
AD  - Anesthesia Operation Department, Zhejiang Hospital, China.
FAU - Qian, Jiang
AU  - Qian J
AD  - Anesthesia Operation Department, Zhejiang Hospital, China.
FAU - Li, Junfeng
AU  - Li J
AD  - School of Basic Medicine, Zhejiang Chinese Medical University, China.
FAU - Wang, Jia
AU  - Wang J
AD  - Neurosurgery Department, Zhejiang Hospital, China.
FAU - Liu, Wenhong
AU  - Liu W
AD  - School of Basic Medicine, Zhejiang Chinese Medical University, China.
FAU - Li, Qinfei
AU  - Li Q
AD  - Anesthesia Operation Department, Zhejiang Hospital, China.
FAU - Wu, Dan
AU  - Wu D
AD  - Anesthesia Operation Department, Zhejiang Hospital, China.
LA  - eng
PT  - Journal Article
PL  - Japan
TA  - J Toxicol Sci
JT  - The Journal of toxicological sciences
JID - 7805798
RN  - 0 (MicroRNAs)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 415SHH325A (Adenosine Monophosphate)
RN  - 67VB76HONO (Dexmedetomidine)
RN  - 9007-43-6 (Cytochromes c)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 3.4.22.- (Caspase 3)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Adenosine Monophosphate/pharmacology
MH  - Animals
MH  - Apoptosis
MH  - Caspase 3/metabolism
MH  - *Chemical and Drug Induced Liver Injury, Chronic
MH  - Cyclooxygenase 2/metabolism
MH  - Cytochromes c/metabolism
MH  - *Dexmedetomidine/pharmacology
MH  - Glutathione/metabolism
MH  - MAP Kinase Signaling System
MH  - *MicroRNAs/genetics/metabolism
MH  - Oxidative Stress
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Rats
MH  - Reactive Oxygen Species/metabolism
MH  - Superoxide Dismutase/metabolism
MH  - bcl-2-Associated X Protein/metabolism
OTO - NOTNLM
OT  - Acute stress-induced liver injury
OT  - Apoptosis
OT  - DEX
OT  - Oxidative stress
OT  - ROS/JNK/p38 signaling pathway
OT  - miR-34a-5p
EDAT- 2022/05/09 06:00
MHDA- 2022/05/11 06:00
CRDT- 2022/05/08 21:43
PHST- 2022/05/08 21:43 [entrez]
PHST- 2022/05/09 06:00 [pubmed]
PHST- 2022/05/11 06:00 [medline]
AID - 10.2131/jts.47.169 [doi]
PST - ppublish
SO  - J Toxicol Sci. 2022;47(5):169-181. doi: 10.2131/jts.47.169.