Effects And Mechanisms Of Dexmedetomidine On Postoperative Cognitive Dysfunction In Aged Rats Undergoing Cardiopulmonary Bypass

Objective: To explore the effects and mechanisms of preuse of dexmedetomidine on postoperative cognitive dysfunction in aged rats undergoing cardiopulmonary bypass.Methods: Ninety Sprague-Dawley rats,aged 18 ~ 20 months,were randomly divided into 3 groups,including cardiopulmonary bypass group with intraperitoneal injection of NS before having a cardiopulmonary bypass surgery(n=30),dexmedetomidine group with intraperitoneal injection of dexmedetomidine doses of 50 ug/kg before having a cardiopulmonary bypass surgery(n=30),and control group without intraperitoneal injection and surgery(n=30).The Morris water maze,the Shuttle box test and Open field test were used to assess the cognitive function of rats.Then we examined the content of Aβ、p-Tau and PSD95 protein in CSF,the hippocampus and prefrontal cortex.Results : Fifty-one rats finished the experiment in whole,including twenty-three rats in cardiopulmonary bypass group,twenty-eight rats in dexmedetomidine group and thirty rats in control group.There was no significant difference in the survival rate in all groups,which are 76.7%,93.3%,100% respectively(P >0.05).1.The Morris water maze(1)The orientation navigation testNo significant differences were observed in the escape latency of rats in three groups before operation(P > 0.05).Compared with cardiopulmonary bypass group,the escape latency of rats in control group and dexmedetomidine group were significantly reduced from the 31 st to 35 th days after operation(P < 0.05).Compared with control group,the escape latency of rats in dexmedetomidine group was prolonged in the 31 st,32nd,34 th,35th days after operation(P <0.05).(2)Spatial probe test Compared with cardiopulmonary bypass group,the frequency of crossing the original platform of rats in control group and dexmedetomidine group were more(P < 0.05).Compared with control group,the frequency of crossing the original platform of rats in dexmedetomidine group was less(P < 0.05).2.The Shuttle box test Compared with cardiopulmonary bypass group,the times of initiative avoiding of rats in control group and dexmedetomidine group were more(P < 0.05),the latency of the initiative and passive avoiding were significantly shorter(P < 0.05).Compared with control group,the times of initiative avoiding of rats in dexmedetomidine group was less(P < 0.05).3.Open field test Compared with cardiopulmonary bypass group,the number of standing on the back legs of rats in control group and dexmedetomidine group were more(P < 0.05),the time that rats spent in the central square was shorter(P < 0.05).Compared with control group,the time that rats spent in the central square in dexmedetomidine group was longer(P < 0.05).4.The content of target protein in cerebrospinal fluidCompared with cardiopulmonary bypass group,the content of protein Aβ and PSD95 in CSF in control group and dexmedetomidine group were higher(P < 0.05),the content of protein p-Tau in CSF were lower(P < 0.05).Compared with control group,the content of protein Aβ in CSF in dexmedetomidine group was lower(P < 0.05).5.The expressing of target protein in brain tissue Compared with cardiopulmonary bypass group,the number of Aβand p-Tau in hippocampus and prefrontal cortex in control group and dexmedetomidine group were reduced(P < 0.05),but the number of PSD95 in hippocampus and prefrontal cortex were significantly more(P < 0.05).Compared with control group,the number of Aβ in hippocampus in dexmedetomidine group was more(P < 0.05),the number of PSD95 in hippocampus was less,the number of Aβ and p-Tau in prefrontal cortex in dexmedetomidine group were increased(P < 0.05)and the number of PSD95 in prefrontal cortex were less(P< 0.05).Conclusion:1.The influence of postoperative cognitive dysfunction after cardiopulmonary bypass in aged rats in the aspect of behavior performance is that impacting spatial learning and memory formation,resulting in a loss of conditional reflex ability,and weakening the ability to adapt in difference environment and cognitive ability.The use of dexmedetomidine before operation can improve their behavior performance.2.The content of Aβ and PSD95 protein in cerebrospinal fluid in aged rats after cardiopulmonary bypass is higher,and the content of p-Tau protein is lower.The use of dexmedetomidine before operation can reduce the change of the extent of target proteins in cerebrospinal fluid.3.The expression of Aβ and p-Tau protein in brain tissue of hippocampus and prefrontal cortex in aged rats after cardiopulmonary bypass is lower,and the expression of PSD95 protein is higher.The use of dexmedetomidine before operation can reduce the abnormal expression of target proteins in cerebrospinal fluid.4.The mechanism that the use of dexmedetomidine before operation can reduce the incidence of postoperative cognitive dysfunction after cardiopulmonary bypass may be adjusted by the expression of Aβ,p-Tau and PSD95.