Remifentanil pretreatment attenuates brain nerve injury in response to cardiopulmonary bypass by blocking AKT/NRF2 signal pathway

Abstract

Objective

This study aimed to explore the effect and mechanism of remifentanil on cardiopulmonary bypass (CPB)-induced cerebral nerve injury.

Methods

After pretreating with remifentanil, or dexmedetomidine (DEX), SD rats were subjected to the CPB for 2 h. The data of body temperature, blood gas and mean arterial pressure (MAP) and hematocrit (HCT) were recorded at different time points. The cerebral tissue water content of rats was determined and immunohistochemical (IHC) and H&E assays on the hippocampal CA1 region of rats was performed. The levels of interleukin (IL)-6, IL-10, soluble protein-100β (S100β) and neuron-specific enolase (NSE) were analyzed by ELISA, and those of the indexes for oxidative stress (malondialdehyde (MDA) and superoxide dismutase (SOD)) were detected by the commercial kits. Morris water maze was used to evaluate the learning and memory abilities. Western blot/qRT-PCR were used to detect the protein/mRNA expressions in hippocampus.

Results

CPB increased the levels/expressions of IL-6, IL-10, S100β, NSE, MDA, cleaved caspase-3, Bax and decreased those of Bcl-2, SOD, p-AKT, HO-1, in serum and parietal cortex tissue, with increased brain water content, lesions in the hippocampal CA1 area, swimming distance, brain nerve injury and decreased escape latency, retention time on platform and times of crossing the platform of rats. The preconditioning of remifentanil or DEX partially attenuated CPB-induced injury and -decreased expressions on p-AKT and HO-1, while further promoting CPB-induced expression of nuclear Nrf2 expression and inhibiting that of cytoplasm Nrf2.

Conclusion

This paper demonstrates that remifentanil preconditioning could partially attenuate CPB-induced brain nerve injury of rats.

Keywords:

• Remifentanil
• cardiopulmonary bypass
• oxidative stress
• apoptosis
• brain nerve injury

Ethical approval

All animal experiments were conducted in accordance with the guidelines of the Chinese Council for Animal Care and Use, and the study was conducted at the First Affiliated Hospital of Guangxi Medical University. Our study has been ethically approved by the Ethics Committee of the First Affiliated Hospital of Guangxi Medical University (FAGMU201812357). All the researchers were dedicated to minimizing the discomfort of the animals throughout the experiment.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The analyzed data sets generated during the study are available from the corresponding author on reasonable request.