The Relationship Between Cerebral Hypoxia And Postoperative Cognitive Dysfunction In Cardiopulmonary Bypassbypass

Objective:There is a high incidence of postoperative cognitive dysfunction in the elderly,while the incidence of postoperative cognitive dysfunction in cardiopulmonary bypass heart surgery is much higher than other types of surgery.The incidence of central nervous system complications such as cognitive dysfunction,stroke and hemiplegia after cardiopulmonary bypass is high.At present,it is believed that the complications of central nervous system after cardiopulmonary bypass are mainly caused by cerebral embolism,cerebral perfusion disorder and central nervous system inflammation.The damage of central nervous system caused by cerebral embolism and cerebral perfusion disorder is closely related to the hypoxia of the whole brain or local brain tissue.Therefore,we suspect that cognitive impairment after CPB is a kind of central nervous system damage,and its mechanism is closely related to brain tissue hypoxia.Objective:To study the changes of cognitive function,cerebral infarction and hypoxia,inflammation,and the damage of blood-brain barrier in rats with cardiopulmonary bypass（CPB）.To explore the relationship between cerebral infarction and hypoxia and postoperative cognitive dysfunction,and the mechanism of postoperative cognitive dysfunction caused by cerebral infarction and hypoxia.Methods:90 healthy adult male SD rats（250g³00g）were randomly divided into two groups:cardiopulmonary bypass group and sham operation group,45 rats in each group.Each group of rats was randomly divided into three groups,15 rats in each group,and the first day,the third day,and the seventh day after the operation.The rats in each group were killed immediately after the completion of the Y-maze experiment.The brain tissues were detected by immunofluorescence The content of hypoxyprobe-1 in hippocampus was detected by Western blot,IL-1β,IL-6 and TNF-αin hippocampus and plasma were detected by ELISA,and the integrity of blood-brain barrier was observed by Evans blue staining.Results:（1）on the first day,the third day and the seventh day of CPB,the spontaneous response rate of Y maze in CPB group was higher than that in sham operation group（P<0.05）;there were differences in the spontaneous response rate of Y maze in CPB group at different time points（F=26.083,P<0.001）,and the spontaneous response rate of Y maze in CPB group was higher than that in the first day（P<0.05）.（2）The results of immunofluorescence showed that the hypoxyprobe-1 was positive in the hippocampal CA3 area of rats in cardiopulmonary bypass group,but negative in the sham operation group.On the first day,the third day and the seventh day,the relative content of hypoxyprobe-1 in the CPB group was higher than that in the sham operation group（P<0.05）;the relative content of hypoxyprobe-1 in the hippocampus of rats in the CPB group was different at different time points（F=46.508,P<0.001）,and the relative content of hypoxyprobe-1 in the hippocampus of rats decreased successively on the first day,the third day and the seventh day after operation（P<0.05）.（4）Immunofluorescence detection showed that Iba-1 was positive in CPB group and negative in sham operation group.（5）The results of ELISA showed that the contents of IL-1β,IL-6 and TNF-αin the hippocampus of the two groups were different(F_IL-1β=63.512,P<0.001;F_IL-6=14.106,P=0.003;F_TNF-α=92.332,P<0.001),and the relative contents of IL-1βand TNF-αin the first day,the third day and the seventh day of CPB were higher than those in the sham operation group(F_IL-1β=63.512,P<0.001;F_IL-6=14.106,P=0.003;F_TNF-α=92.332,P<0.001);the relative contents of IL-6 in the first day and the seventh day of CPB were higher than those in the sham operation group（P<0.05）;there was no difference in the contents of IL-1β,IL-6 and TNF-αin the hippocampus of the two groups at different time points(F_IL-1β=0.545,P=0.594;F _IL-6=1.194,P=0.337;F_TNF-α=1.757,P=0.214).The results of ELISA showed that the contents of IL-1β,IL-6 and TNF-αin the plasma of the two groups were different(F_IL-1β=40.849,P<0.001;F_IL-6=37.924,P<0.001;F_TNF-α=107.750,P<0.001).On the first day and the seventh day,the relative contents of IL-1βin the cardiopulmonary bypass group were higher than those in the sham operation group（P<0.05）.On the first day,the relative contents of IL-6 in the cardiopulmonary bypass group were higher than those in the sham operation group（P<0.05）.On the first day,the third day and the seventh day after the operation,the relative contents of TNF-αin the plasma of the rats were higher than those in the sham operation group（P<0.05）;there was no difference in the contents of IL-1β,IL-6 and TNF-αin the plasma of the two groups at different time points(F_IL-1β=1.573,P=0.247;F_IL-6=0.739,P=0.498;F_TNF-α=0.047,P=0.955).（6）Evans blue staining showed that on the first day,the third day and the seventh day,the content of Evans blue in the brain tissue of the CPB group was higher than that of the sham operation group（P<0.05）;there were differences in the content of Evans blue in the brain tissue of the CPB group at different time points in the CPB group（F=82.919,P<0.001）,and the content of Evans blue in the brain tissue of the CPB group on the first day and the seventh day after the operation was higher than that on the third day after the operation（P<0.05）.Conclusion:（1）Postoperative cognitive dysfunction and brain tissue hypoxia induced by cardiopulmonary bypass in rats,and cardiopulmonary bypass also leads to inflammatory reaction and damage of blood-brain barrier;（2）hypoxia of brain tissue after cardiopulmonary bypass may be the cause of cognitive dysfunction;（3）hypoxia of brain tissue may lead to post-operative cognitive dysfunction through inflammation of central nervous system and destruction of blood-brain barrier.