To study the effect of dexmedetomidine on cognitive function in rats with cognitive impairment after partial hepatectomy and its mechanism.60 SD rats were randomly divided into 4 groups (n = 15): blank control group (CG group), sham operation group (Sham group), cognitive impairment model group (POCD group), and dexmedetomidine + cognitive impairment model group (DEX group). Rats in the POCD group underwent left lobe hepatectomy and intraperitoneal injection of the same amount of normal saline after resuscitation. Rats in the DEX group underwent left lobe hepatectomy and intraperitoneal injection of dexmedetomidine 50 μg/kg. Group CG was not operated on and the same amount of normal saline was injected intraperitoneally. In the Sham group, liver resection was not allowed after the abdominal incision, and normal saline was injected intraperitoneally. Rats were injected every 24 hours for 5 consecutive days. Morris water maze (MWM) were used to evaluate the effects of dexmedetomidine on learning and memory ability of POCD rats. TUNEL method was used to detect apoptotic neurons in the hippocampus. INOS, Arg-1, IL-6, and TNF-αexpression levels were detected. Western blot detects the expression level of TNF-α, Bcl-2, and NF-κB protein.Compared with the CG group, the escape latency of the other three groups was prolonged on the 5th day after the operation, and the number of crossing the platform was reduced. Compared with the Sham group, the escape latency of the POCD group and DEX group was significantly prolonged, and the number of crossing the platform was significantly reduced on day 5 (P < 0.05). Compared with the POCD group, the DEX group shortened the escape latency and increased the number of crossing the platform on the 5th day (P < 0.05). It shows that the spatial learning and memory function of rats has been restored to a certain extent.The number of iNOS and Arg-1 positive cells in the POCD group and DEX group was higher than that in the control group, and the number of Arg-1 positive cells in the DEX group was higher than that in the POCD group (P < 0.05). Western blot results the expression of Bcl-2 and NF-κB protein in POCD group, and DEX group was higher than that of the sham group (P < 0.05). The expression of Bcl-2 and NF-κB protein was the most in POCD group. The expression of Bcl-2 and NF-κB protein in DEX group was lower than that in POCD group (P < 0.05).Behavioral results showed that the learning and cognitive ability of POCD model rats after hepatectomy was impaired, and inflammatory factors and activated microglia were found in the hippocampus of POCD rats. Dexmedetomidine may improve the brain function of POCD rats by inhibiting neuronal apoptosis,partly through NF-κB apoptosis pathway.Copyright © 2022 Zitan Zhang and Huiqun Jia.