Effects of dexmedetomidine on anxiety and neuroinflammation in the hippocampus induced by fractures in rats
Objective To establish a rat fracture model to study the regulatory effects of dexmedetomidine on anxiety and hippocampal neuroinflammation caused by fractures in rats.Methods Forty adult male Wistar rats were randomly divided into four groups in a free drinking water mode:the control group(blank control group),DEX group(dexmedetomidine group),surgery group(right femur osteotomy),and surgery+DEX group(intraperitoneally injected with 12 μg/kg DEX after fracture).At 6 h,24 h and 7 d after the establishment of the model,the anxiety of the rats was measured via fright response,the expressions of inflammatory factors(TNF-α,IL-1 β,IL-6)in the serum and hippocampal tissue of the rats were detected by ELISA,and the apoptotic cells in the hippocampus were quantified by TUNEL staining.Western blot was used to detect the expressions of TNF-α,IL-1β,IL-6,nNOS,NOX2,4-HNE,Bax and Bcl-2 proteins in the hippocampus.Results Compared with the control group,the serum levels of TNF-α,IL-1β and IL-6 and the mRNA levels of TNF-α,IL-1 β and IL-6 in the hippocampus of the operation group were increased(P<0.001),and the number of apoptotic cells was increased.The expression levels of Bcl-2(P<0.001)and nNOS(P=0.001)in hippocampus were decreased,while the expression levels of Bax(P<0.001)and 4-HNE(P=0.001),NOX2(P=0.003)and ROS(P=0.009)in hippocampus were increased.The serum levels of TNF-α,IL-1 β and IL-6 and the mRNA levels of TNF-α,IL-1 β and IL-6 in hippocampal tissue were decreased in the operation+DEX group(P<0.001),the number of apoptotic cells and the level of Bax protein were significantly decreased(P=0.008).The levels of 4-HNE(P<0.001),NOX2(P<0.001)and ROS(P=0.008)in hippocampus were decreased,while the expression levels of Bcl-2(P=0.005)in neurons and nNOS(P<0.001)in hippocampus were increased.Conclusion Dexmedetomidine can significantly improve the anxiety state,reduce neuroinflammation and neuronal apoptosis in rats with fractures.