Objective To investigate the effect of dexmedetomidine (DEX) on early cognitive dysfunction after hepatic lobectomy by regulating microRNA-182-5p/brain-derived neurotrophic factor (miR-182-5p/BDNF) axis in rats.

Methods Sixty specific pathogen free(SPF) SD male rats were randomly divided into control group, model group, DEX low dose treatment group (25 μg/kg), DEX medium dose treatment group (50 μg/kg), DEX high dose treatment group (100 μg/kg), and DEX+ miR-182-5p mimic group, with 10 rats each group. The rats in the model group were anesthetized with sevoflurane and then underwent partial hepatectomy. The rats in DEX low-, medium-, and high-dose treatment groups were injected with DEX (25, 50, and 100 μg/kg) intraperitoneally and inhaled sevoflurane for 30 minutes before partial hepatectomy. DEX + miR-182-5p mimic group rats were treated with the same method as DEX high-dose treatment group, and miR-182-5p mimic (50 μg) was injected through tail vein every 2 days after operation. Rats in the control group were intraperitoneally injected with 2 mL/kg normal saline, then anesthetized by inhalation of sevoflurane for 2 hours. Morris water maze test and Neurological Severity Scale (NSS) were used to evaluate the postoperative cognitive function and neurological function damage of rats in each group. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to measure the level of miR-182-5p in rat hippocampus. The protein expression level of BDNF in hippocampus was determined by western blot. The binding region of miR-182-5p and BDNF 3'UTR was analyzed by bioinformatics, and the targeting relationship between miR-182-5p and BDNF was detected by dual luciferase reporter gene assay.

Results The results showed that compared with the control group, the escape latency of Morris water maze test in the model group was significantly prolonged at 2 to 5 days after operation (P < 0.05), and the NSS scores in the model group were significantly increased at 1, 3 and 7 d after operation (P < 0.05). Compared with the model group, the rats in the DEX treatment group had significantly shorter escape latency of Morris water maze test at 2 to 5 days after operation, and significantly lower NSS scores at 3 and 7 days after operation in a dose-dependent manner (P < 0.05). Compared with the DEX high-dose treatment group, the DEX + miR-182-5p mimic group had significantly prolonged escape latency of Morris water maze test at 2 to 5 days after operation, and significantly increased NSS scores at 3 and 7 days after operation (P < 0.05). Compared with the control group, the level of miR-182-5p in the hippocampus of the model group was significantly increased, and the level of BDNF was significantly decreased (P < 0.05). Compared with the model group, the DEX treatment group had a significant reduction in the level of miR-182-5p and a significant increase in the level of BDNF in the hippocampus after surgery in a dose-dependent manner (P < 0.05). Compared with the DEX high-dose treatment group, the DEX + miR-182-5p mimic group had a significant increase in the level of miR-182-5p and a significant reduction in the level of BDNF (P < 0.05). The dual luciferase reporter gene assay verified the targeted binding of miR-182-5p to BDNF.

Conclusion DEX improves early cognitive dysfunction in rats after hepatic lobectomy by inhibiting miR-182-5p and increasing BDNF levels.