Abstract: Objective To establish a rat fracture model to study the regulatory effects of dexmedetomidine on anxiety and hippocampal neuroinflammation caused by fracture in rats. 
Methods A total of 40 adult male Wistar rats were randomly divided into control group, dexmedetomidine group, operation group (right femur osteotomy), and operation + dexmedetomidine group (12 μg/ kg intraperitoneal injection of dexmedetomidine after fracture) using free drinking water mode. The rat fracture model was established. On 6 h, 24 h, and 7 d after the successful establishment of the model, the anxiety of the rats was tested by scare-response, and the expression levels of inflammatory factors ［tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6)］ in the serum and hippocampal tissue of the rats were detected by enzyme-linked immunosorbent assay （ELISA）. Apoptotic cells in hippocampal tissues were quantitatively analyzed by TUNEL staining, and the expressions of TNF-α, IL-1β, IL-6, reactive oxygen species (ROS), neuronal nitric oxide synthase(nNOS), nicotinamide adenine dinucleotide phosphate (NOX2), 4-hydroxynonenal (4-HNE), BCL2-Associated X (Bax) and B-cell lymphoma-2 (Bcl-2) in hippocampal tissues were detected by Western blot. Results As the intensity of acoustic stimulation increased from sub-threshold (74 dB) to near threshold (90 dB) to over threshold (110 dB), the acoustic startle response(ASR) increased significantly. At the threshold of 74, 90 and 100 dB, the ASR of dexmedetomidine group was lower than that of control group, but higher in operation group than in control group and dexmedetomidine group; The ASR was higher in operation + dexmedetomidine group than in dexmedetomidine group but lower than that of operation group (P＜0.05). The serum levels of TNF-α, IL-6 and IL-1β in dexmedetomidine group were lower than those in control group, but significantly higher in operation group than in control group and dexmedetomidine group; the serum levels of TNF-α, IL-6 and IL-1β in operation + dexmedetomidine group were higher than those in dexmedetomidine group, but lower than that in operation group (P＜0.05). The expression levels of TNF-α, IL-6 and IL-1β in the hippocampus of dexmedetomidine group were significantly lower than those of control group, but significantly higher in operation group than in control group and dexmedetomidine group. The expression levels of TNF-α, IL-6 and IL-1β in the hippocampus of operation + dexmedetomidine group were higher than those of operation group, but lower than those of operation group (P＜0.05). TUNEL staining showed that the number of apoptotic cells in dexmedetomidine group decreased significantly, and the number in operation group increased significantly. The expression level of Bax in dexmedetomidine group was significantly lower than that in the control group, while the expression level of Bcl-2 was higher than that in the control group; the expression level of Bax in operation group was significantly higher than that in the control group and dexmedetomidine group, while the expression level of Bcl-2 was significantly lower than that in the control group and dexmedetomidine group. The expression level of Bax in the operation group + dexmedetomidine group was higher than that in the dexmedetomidine group, but lower than that in the operation group. The expression level of Bcl-2 was lower than that of dexmedetomidine group but higher than that of operation group (P＜0.05). The hippocampal ROS level was lower in dexmedetomidine group than in control group, lower in operation group than in control group and dexmedetomidine group, and higher in operation + dexmedetomidine group than in operation group, but lower than that of operation group, with statistical significance (P＜0.05). The expression of NOX2 and 4-HNE protein in hippocampus of dexmedetomidine group was lower than that of control group, while the expression of nNOS protein was higher than that of control group. The expression of NOX2 and 4-HNE protein in hippocampus of operation group was higher than that of control group and dexmedetomidine group, while the expression of nNOS protein was lower than that of control group and dexmedetomidine group. The expression of NOX2 and 4-HNE protein in hippocampus of operation + dexmedetomidine group was higher than that of dexmedetomidine group, but lower than that of operation group, while the expression of nNOS protein was lower than that of dexmedetomidine group but higher than that of operation group, with statistical significance (P＜0.05). 
Conclusion Dexmedetomidine can significantly improve the anxiety state, reduce neuroinflammation and neuronal apoptosis in rats with fracture. 

Key words: fracture, dexmedetomidine, anxiety