Dexmedetomidine inhibits cerebral nerve cell apoptosis after cerebral hemorrhage in rats via the Nrf2/HO-1/NQO1 signaling pathway

G. Shao

Department of Anesthesiology, The People’s Hospital of Danyang, Affiliated Danyang Hospital of Nantong University, Danyang, China. 386704016@qq.com

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• Neurology

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.

 

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