Exploration on the mechanism of dexmedetomidine alleviating diabetic brain injury by regu-lating PPARγ/NF-κB pathway

Objective:To investigate the effect and mechanism of dexmedetomidine (DEX) on brain injury in type 2 diabetic rats.Methods:48 SPF male SD rats were randomly divided into 3 groups: normal group (con-trol group), diabetes mellitus group (DM group) and DEX group, with 16 rats in each group.Except for the con-trol group, 28 SD rats in the other groups were fed with high-fat diet for 4 weeks and then streptozotocin (STZ)was injected intraperitoneally at a single dose of 40 mg/kg to establish type 2 diabetes mellitus model.Random blood glucose≥16.7 mmol/L was defined as successful modeling after 4 weeks.The rats in the DEX group were intraperitoneally injected with 40μg/kg DEX once a day for 2 weeks after the DM model was successfully estab-lished, while the rats in the DM group were intraperitoneally injected with the same amount of 0.9% normal sa-line.Fasting blood glucose, body weight, and survival rate of rats in each group were observed and recorded.Af-ter the modeling was completed, the rats were sacrificed, and the brain cortex and hippocampal tissues were col-lected.Hematoxylin and eosin (HE) staining was used to detect histopathological changes in rat brain tissue.Western blotting and immunohistochemistry were used to detect the expressions of p-PPARγ and NFκB.Results:Compared with the control group, the rats in the DM group showed increased blood glu-cose and decreased body weight, and some degree of structural destruction of brain tissue and inflammatory cell infiltration were observed.In addition, the expression of p-PPARγ protein decreased(P< 0.05), and NF-κB expression increased(P< 0.05).However, the above chang-es were reversed after the administration of DEX treatment.Compared with the DM group, the DEX group showed decreased blood glucose, alleviated brain tissue injury, increased P-PPARγ protein expression and de-creased NF-κB protein expression (all P< 0.05).Conclusion:DEX may alleviate brain injury in type 2 diabetic rats by regulating the PPARγ/NF-κB signaling pathway.