PMID- 35856346
OWN - NLM
STAT- MEDLINE
DCOM- 20220721
LR  - 20220817
IS  - 2284-0729 (Electronic)
IS  - 1128-3602 (Linking)
VI  - 26
IP  - 13
DP  - 2022 Jul
TI  - Dexmedetomidine inhibits cerebral nerve cell apoptosis after cerebral hemorrhage 
      in rats via the Nrf2/HO-1/NQO1 signaling pathway.
PG  - 4574-4582
LID - 29178 [pii]
LID - 10.26355/eurrev_202207_29178 [doi]
AB  - OBJECTIVE: To investigate the effect of dexmedetomidine on the apoptosis of 
      cerebral nerve cells after cerebral hemorrhage (CH) in rats and its molecular 
      mechanism. MATERIALS AND METHODS: The rat model of CH was established by 
      autologous blood injection. A total of 60 specific pathogen-free (SPF)-grade rats 
      were randomly divided into sham-operation group, model group and dexmedetomidine 
      group, and each group involved 20 rats. Rat brain water content was compared 
      among the three groups. Besides, rat neurological function of the three groups 
      was evaluated at 3, 5 and 7 d after operation by neurological function scoring. 
      Western blotting assay was adopted to detect protein levels of apoptosis-related 
      genes [B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax)] in rat 
      brain tissues in the three groups. Moreover, the apoptosis level in the brain 
      tissues in the groups was measured through terminal deoxynucleotidyl 
      transferase-mediated dUTP nick end labeling (TUNEL) assay. Biochemical tests were 
      conducted to determine activities of reduced glutathione (GSH), superoxide 
      dismutase (SOD) and malondialdehyde (MDA) in the brain tissues among the three 
      groups. Furthermore, the activation of the nuclear factor erythroid 2-related 
      factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/NAD(P)H quinone oxidoreductase 1 (NQO1) 
      signaling pathway in the brain tissues of the three groups of rats was examined 
      via Western blotting assay. An in vitro oxygen-glucose deprivation (OGD) model 
      was prepared using SH-SY5Y cells. In addition, Nrf2 was intervened in SH-SY5Y 
      cells by small hairpin ribonucleic acid (shRNA) transfection. Finally, flow 
      cytometry and Annexin V/PI assay were performed to detect the response of cells 
      to dexmedetomidine in OGD + dexmedetomidine + sh-Nrf2 group. RESULTS: The brain 
      water content and the neurological function score at 3, 5 and 7 d after operation 
      were remarkably reduced in dexmedetomidine group compared with those in model 
      group. The results of Western blotting and TUNEL assays indicated that 
      dexmedetomidine group had a notably lowered apoptosis level in the brain tissues. 
      Additionally, the biochemical test results manifested that activities of GSH and 
      SOD were enhanced and that of MDA decreased in the brain tissues of 
      dexmedetomidine group. Protein levels of Nrf2, HO-1 and NQO1 in the brain tissues 
      were distinctly higher in dexmedetomidine group than those in model group. 
      According to the results of flow cytometry, the apoptosis rate in OGD + 
      dexmedetomidine + sh-Nrf2 group rose prominently compared with that in OGD + 
      dexmedetomidine group. CONCLUSIONS: Dexmedetomidine inhibits the nerve cell 
      apoptosis in rat brain tissues by activating the Nrf2/HO-1/NQO1 signaling pathway 
      in rat CH models.
FAU - Shao, G
AU  - Shao G
AD  - Department of Anesthesiology, The People's Hospital of Danyang, Affiliated 
      Danyang Hospital of Nantong University, Danyang, China. 386704016@qq.com.
LA  - eng
PT  - Journal Article
PL  - Italy
TA  - Eur Rev Med Pharmacol Sci
JT  - European review for medical and pharmacological sciences
JID - 9717360
RN  - 0 (NF-E2-Related Factor 2)
RN  - 059QF0KO0R (Water)
RN  - 67VB76HONO (Dexmedetomidine)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 1.6.5.2 (NAD(P)H Dehydrogenase (Quinone))
RN  - EC 1.6.5.2 (NQO1 protein, human)
RN  - EC 1.6.5.2 (NQO1 protein, rat)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Cerebral Hemorrhage/drug therapy
MH  - *Dexmedetomidine/pharmacology
MH  - Heme Oxygenase-1/metabolism
MH  - Humans
MH  - NAD(P)H Dehydrogenase (Quinone)/genetics
MH  - NF-E2-Related Factor 2/metabolism
MH  - *Neuroblastoma
MH  - Neurons/metabolism
MH  - Oxidative Stress
MH  - Rats
MH  - Signal Transduction
MH  - Superoxide Dismutase/metabolism
MH  - Water
EDAT- 2022/07/21 06:00
MHDA- 2022/07/22 06:00
CRDT- 2022/07/20 06:23
PHST- 2022/07/20 06:23 [entrez]
PHST- 2022/07/21 06:00 [pubmed]
PHST- 2022/07/22 06:00 [medline]
AID - 29178 [pii]
AID - 10.26355/eurrev_202207_29178 [doi]
PST - ppublish
SO  - Eur Rev Med Pharmacol Sci. 2022 Jul;26(13):4574-4582. doi: 
      10.26355/eurrev_202207_29178.