DEXMEDETOMIDINE ALLEVIATES HIPPOCAMPAL NEUROINFLAMMATION AND COGNITIVE IMPAIRMENT INDUCED BY ANESTHESIA THROUGH SIRT1

Hu Sun^{1, #}, Tao Wang¹, Huan Cao², Xiaofang Chen¹, Liang Zhang^{2, *}, Zhixin Xu^{1, *}

¹Department of Anesthesiology, The Second Affiliated Hospital of Hainan Medical University, Haikou 570311, Hainan Province, China - ²Department of Anesthesiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 511447, Guangdong Province, China

Objective: To investigate the effect and mechanism of dexmedetomidine (DEX) on hippocampal neuroinflammation and cognitive impairment induced by anesthesia in aged rats. 

Methods: Sixty 18-month-old SD rats were randomly divided into a control group, a model group and a DEX group. Splenectomies were performed in the model group and the DEX group, while no treatment was given in the control group. Dexamethasone was injected into the tail vein of the dexamethasone group before the operation, and a Y maze test was performed at 9 AM on the first, third and seventh days after operation. The pH value, PaO₂, PaCO₂ and other blood gas analysis indexes of mice in each group under anesthesia were detected, and the serum IL-1 was detected by enzyme-linked immunosorbent assay β,TNF- α Level. A western blot was used to detect SIRT1 and NF in the hippocampus- κ B protein expression. 

Results: There was no significant difference in pH, PaO₂ and PaCO₂ among the three groups (P>0.05). There was no significant difference in shuttle times among the three groups on the first, third, or seventh day after the operation (P>0.05). On the first and third days after the operation, the alternation score rates of the model group and the DEX group were significantly lower than that of the control group, and the alternation score rate of the DEX group was significantly higher than that of the model group (P<0.05). The levels of IL-1 in the model group and the DEX group were significantly increased on the first and third days after the operation β. The level of IL-1 in the DEX group was significantly higher than that in the control group β. The level was significantly lower than that of the model group (P<0.05). On the first and third days after the operation, TNF - α in the model group and the DEX group decreased- α. The level of TNF in the DEX group was significantly higher than that in the control group- α. The level was significantly lower than that of the model group (P<0.05). The SIRT1 protein in the model group and the DEX group was significantly lower than that in the control group- κ. The expression of the SIRT1 protein in the DEX group was significantly higher than that in model group- κ. Protein B was significantly lower than that in model group (P<0.05). 

Conclusion: DEX can inhibit the inflammatory reaction and improve the postoperative cognitive function of aged rats after anesthesia, which may be related to the regulation of SIRT1 pathway related proteins by DEX.