Study On The Effect And Mechanism Of Esketamine In Improving Postoperative Depressio

PART Ⅰ Effects of a low dose of S-ketamine on postoperative depression after bariatric surgeryBackground Studies have shown that the incidence of depression after bariatric and metabolic surgery is as high as 35%,which seriously affects the postoperative rehabilitation of patients.Previous studies have shown that low-dose S-ketamine has a significant effect on treatmentresistant depression,but for perioperative depression,the results of different centers are controversial.As it is well known that anesthesia can regulate brain metabolism and activity,we hypothesize that anesthetic drugs change brain functional activity and thus affect the antidepressant effect of S-ketamine.Therefore,the aim of this study is to investigate whether lowdose S-ketamine can improve post-bariatric and metabolic surgery depression and whether its antidepressant effect is affected by anesthesia status.Methods This study was a randomized,double-blind,controlled study.120 patients undergoing bariatric and metabolic surgery were randomly divided into 3 groups(n = 40): S-ketamine administration after anesthesia induction group(group A),S-ketamine administration before anesthesia induction group(group B)and control group(group C).Group B was given Sketamine 0.2mg/kg 2 h before anesthesia induction,group A was given S-ketamine 0.2mg/kg after anesthesia induction,and group C was given 0.9% normal saline after anesthesia induction.The primary outcome measures were PHQ-9 depression score and plasma BDNF level.The secondary outcome measures were postoperative recovery,including Qo R-15 score,VAS pain score,extubation time,return to ward time,first exhaust time,postoperative hospital stay,length of hospital stay,and the incidence of adverse reactions such as nausea,vomiting,and dizziness.Results On the first day after operation,the PHQ-9 scores of group A and C were significantly higher than those of group B(F=6.834,P<0.05),but there was no significant difference between group A and group C(F=6.834,P>0.05).At the corresponding time points,the plasma BDNF concentration in group B was higher than that in group C and group A(F=12.185,P<0.05).There was no significant difference between groups A and C(F=12.185,P>0.05).The PHQ-9 score and plasma BDNF score of group B were better than those of group C on the second day after operation(F=3.678,F=10.044,P<0.05).Further correlation analysis showed that PHQ-9 scores were moderately correlated with plasma BDNF concentration in the three groups(r=-0.56,P<0.05).In terms of postoperative pain and postoperative recovery,group B was significantly better than group C.Conclusions Low doses of S-ketamine can remove the postoperative depression in patients undergoing bariatric surgery,but its antidepressant effects may be influenced by anesthesia.PART Ⅱ The mechanism of BDNF methylation in the improvement of postoperative depression by S-ketamineObjective: In the first part of the study,it has been confirmed that S-ketamine can improve the depressive state after surgery,but the mechanism is still unclear.Previous studies have shown that DNA methyltransferases(DNMTs)regulate the methylation of BDNF gene,inhibit the expression of BDNF gene in the medial frontal cortex and hippocampus,and play an important role in depression.The aim of this study is to determine whether the occurrence of postoperative depression is related to the inhibition of BDNF gene expression by DNMTs and whether Sketamine can improve postoperative depression through DNMTs.Methods: In this study,we used preoperative anxiety and partial hepatectomy to establish a SD rat model of postoperative depression.The depression-like behaviors of the rats were observed by behavioral tests such as sucrose preference,forced swimming test,and open field test.The expressions of BDNF and DNMTs in the medial frontal cortex and hippocampus were detected by q RT-PCR and Western blot.To further investigate whether the occurrence of postoperative depression is related to DNMTs,we used RG108,an inhibitor of DNMTs,to intervene in rats with postoperative depression.At the same time,to explore whether S-ketamine can improve postoperative depression through DNMTs and whether the antidepressant effect is affected by the state of anesthesia,we injected 15mg/kg S-ketamine intraperitoneally 2h before and after anesthesia to treat postoperative depression rats.Results: Compared with the control group,the rats in the postoperative depression group showed decreased sucrose preference,prolonged stationary swimming time,decreased total distance in open field and decreased expression of BDNF gene,but the expression of DNMTs was also decreased.Compared with the model group,intraperitoneal injection of RG108 did not significantly improve sucrose preference,forced swimming rest time,total open field movement distance,and BDNF gene expression in the rats.Compared with the model group,the injection of S-ketamine before anesthesia can improve the depression-like behavior and the low expression of BDNF in the postoperative depression rats,but the injection of S-ketamine after anesthesia has no significant improvement in the depression-like behavior and the expression of BDNF.Conclusion: Postoperative depression decreases BDNF expression,However,the mechanism may not be related to DNMTs.S-ketamine can improve postoperative depression,but its antidepressant effect is affected by the state of anesthesia.