Ling Zhang1, Qian Zhou1, Chun-Li Zhou2. 1. Department of Anesthesiology, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, China. 2. Department of Anesthesiology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China.
Abstract
OBJECTIVE: To explore the effect of RTA-408 on the propofol-induced cognitive impairment of neonatal mice via regulating Nrf2 and NF-κB p65 nuclear translocation. METHODS: C57BL/6 neonatal mice were randomized into intralipid, propofol, vehicle + propofol, and RTA-408 + propofol groups. The learning and memory ability was inspected by Morries water maze (MWM) test. TUNEL staining was performed to examine the apoptosis of neurons in hippocampus. The gene and protein expressions in hippocampus were detected by immunohistochemistry, qRT-PCR, or Western blotting. The activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) were tested by the corresponding kits. RESULTS: Propofol prolonged escape latency of mice, decreased the times of crossing the platform, and shortened the time of staying in the target quadrant, while RTA-408 treatment improved the above-mentioned situation. Besides, Nrf2 protein in hippocampus of mice induced by propofol was decreased with the increased NF-κB p65 nuclear translocation, which was reversed by RTA-408. Meanwhile, RTA-408 decreased the apoptosis of neurons accompanying with the down-regulation of Caspase-3 and the up-regulations of neuronal-specific nuclear protein (NeuN), microtubule-associated protein 2 (Map2), Ca2 + /Calmodulin-dependent Protein Kinase II (CaMKII), and parvalbumin (PV) immunostaining in hippocampus. Besides, propofol-induced high levels of proinflammatory cytokines and antioxidase activities in hippocampus were reduced by RTA-408. CONCLUSION: RTA-408 improved propofol-induced cognitive impairment in neonatal mice via enhancing survival of neurons, reducing the apoptosis of hippocampal neurons, mitigating the inflammation and oxidative stress, which may be correlated with the activation of Nrf2 and the inhibition of NF-κB p65 nuclear translocation.
OBJECTIVE: To explore the effect of RTA-408 on the propofol-induced cognitive impairment of neonatal mice via regulating Nrf2 and NF-κB p65 nuclear translocation. METHODS: C57BL/6 neonatal mice were randomized into intralipid, propofol, vehicle + propofol, and RTA-408 + propofol groups. The learning and memory ability was inspected by Morries water maze (MWM) test. TUNEL staining was performed to examine the apoptosis of neurons in hippocampus. The gene and protein expressions in hippocampus were detected by immunohistochemistry, qRT-PCR, or Western blotting. The activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) were tested by the corresponding kits. RESULTS: Propofol prolonged escape latency of mice, decreased the times of crossing the platform, and shortened the time of staying in the target quadrant, while RTA-408 treatment improved the above-mentioned situation. Besides, Nrf2 protein in hippocampus of mice induced by propofol was decreased with the increased NF-κB p65 nuclear translocation, which was reversed by RTA-408. Meanwhile, RTA-408 decreased the apoptosis of neurons accompanying with the down-regulation of Caspase-3 and the up-regulations of neuronal-specific nuclear protein (NeuN), microtubule-associated protein 2 (Map2), Ca2 + /Calmodulin-dependent Protein Kinase II (CaMKII), and parvalbumin (PV) immunostaining in hippocampus. Besides, propofol-induced high levels of proinflammatory cytokines and antioxidase activities in hippocampus were reduced by RTA-408. CONCLUSION: RTA-408 improved propofol-induced cognitive impairment in neonatal mice via enhancing survival of neurons, reducing the apoptosis of hippocampal neurons, mitigating the inflammation and oxidative stress, which may be correlated with the activation of Nrf2 and the inhibition of NF-κB p65 nuclear translocation.
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