The Effect And Mechanism Of Dexmedetomidine Onperioperative Neurocognitive Disorders

Objective: To investigate the therapeutic effect of dexmedetomidine on perioperative neurocognitive disorders in aged rats and its dosage-effect relationship.To explore the important role of triggering receptor expressed on myeloid cells 2 in the dexmedetomidine treatment of perioperative neurological dysfunction in aged rats.Methods: Fourty-eight specific pathogen free old male SD rats(18 months)Weighted500-700 g were adaptive fed for one week.After 6 days of Morris water maze navigation experiment,These aged rats were randomly divided into six groups,conclude Sham group,PND group,PND+Saline group,PND+Dexmedetomidine 1ug/kg group,PND+Dexmedetomidine 10ug/kg group,PND+ Dexmedetomidine 100 ug/kg group,The PND model was established by internal fixation of tibial fracture on the 7th day,The sham group cut through the skin of the calf and stitched it.At 24 h after the operation,dexmedetomidine or equivalent normal saline were given.The change of cognitive function after the operation 24 h and 48 h were detected by the Morris water maze experiment.The hippocampus of rats were taken 48 hours after surgery.The expression of TREM2 in hippocampus were detected use Western Blot technique,and Enzyme-Linked ImmunoSorbent Assay(ELISA)was used to detect the expression of TNF-??IL-1? in peripheral blood after treatment.Resluts: With the extension of learning time,the escape latency of the old rats was significantly shortened as the results of Morris water maze navigation experiment show(P<0.05).24 h after internal fixation of tibial fracture,compared with Sham group,PND group,PND+ Saline group,PND + Dexmedetomidine 1ug/kg group,PND + Dexmedetomidine10ug/kg group,PND + Dexmedetomidine 100 ug/kg group escape latency was prolonged,the target quadrant residence time was significantly shortened,and the original platform crossing times were significantly reduced.(P<0.05),24 h after treatment with dexmedetomidine,Compared with the PND group,PND + Dexmedetomidine 1ug/kg group,PND +Dexmedetomidine 10ug/kg group,PND + Dexmedetomidine 100 ug/kg group escape latency significantly shortened,target quadrant residence time ratio significantly increased,escape platform crossing times significantly increased(P<0.05),In the PND+ saline group,there was no significant change in the escape latency,escape platform crossing times and target quadrant residence time ratio(P> 0.05).Among them,The change of escape latency,escape platform crossing timesand target quadrant residence time ratio was more obvious in the PND + Dexmedetomidine 10ug/kg group and PND + Dexmedetomidine 100ug/kg group.Compared with Sham group,the expression of TREM2 in the hippocampus in the PND group was significantly reduced,and the inflammatory factor TNF-? and IL-1? in peripheral blood was significantly increased(P<0.05).Compared with the PND group,the expression of TREM2 in hippocampus was increased in PND + Dexmedetomidine 1ug/kg group,PND + Dexmedetomidine 10ug/kg group,PND+ Dexmedetomidine 100 ug/kg group,The levels of inflammatory cytokines TNF-? and IL-1? in peripheral blood were significantly decreased in PND + Dexmedetomidine 1ug/kg group,PND + Dexmedetomidine10ug/kg group,PND+ Dexmedetomidine 100 ug/kg group(P<0.05).Among them,the level of inflammatory factors have a significant decrease and the level of TREM2 expression increased significantly in the PND + Dexmedetomidine 10ug/kg group and PND +Dexmedetomidine 100 ug/kg group.Conclusions: Dexmedetomidine treatment can improve the cognitive dysfunction of elderly rats caused by internal fixation of tibial fractures,and the better treatment effect is10?g/kg.Its mechanism is related to dexmedetomidine's up-regulation of TREM2 expression and inhibition of inflammatory response.