| Part 1 The mechanism of neurogenic inflammation in dexmedetomidine improving learning and memory impairment in rats after partial hepatectomy Objective:To explore the effect of dexmedetomidine on learning and memory ability and neurogenic inflammation in rats with partial hepatectomy.Methods:1.Preparation of the PND model.2.Animal Grouping and Treatment.Seventy-five 18-month-old SD rats weighing 450-600 g,male,were randomly divided into four groups(n=15):A:Control group(CG group)(intraperitoneal injection of the same dose of normal saline for 1-5 days)B:Sham operation group(Sham group)(rats were anesthetized and abdominal incision was performed without hepatectomy,then the incision was sutured,and the same dose of normal saline was injected intraperitoneally 1-5days after modeling)C:Cognitive impairment model group(PND group)(intraperitoneal injection of the same dose of normal saline 1-5 days after modeling)D:Dexmedetomidine+cognitive impairment model group(Dex group)(intraperitoneal injection of dexmedetomidine 50(μg/kg)per day 1-5days after modeling)3.Behavioral experiment After the surgery,6、 7、 8、 9、 10、 11 days to perform Morris water maze experiment training.To investigate the feasibility of the PND model of rats by partial hepatectomy and the protective effects of dexmedetomidin on learning and memory ability of rats. 4.By HE staining to observe rat cortex and hippocampus tissue and nerve cells morphological changes.5.TUNEL staining positive cells were used to observe the neuronal apoptosis in the hippocampal nerve tissue.6.Immunohistochemical detection of TNF-α in rat hippocampus.7.The RT-qPCR method to detect the mRNA expression of iNOS and Arg-1 in hippocampus.Results:1.The results of behavioral experiment.The experimental results showed that compared with the CG group,the escape latency of the PND and Dex groups was prolonged from the 6th day after operation,and the number of crossing the platform was reduced.Compared with Sham group,the escape latency of PND group and Dex group was significantly prolonged,and the number of crossing the platform was significantly reduced(P<0.05).The results show that the PND model was feasible.Compared with the PND group,the Dex group shortened the escape latency and increased the number of crossing the platform(P<0.05).It shows that,to a certain extent,the learning and memory function of rats have been restored by dexmedetomidine.2.HE staining results CG group had full hippocampal tissue structure,close and regular arrangement between cells,complete matrix without vacancy,and consistent staining of all parts.There was no significant change in neuron morphology in Sham group.In the PND group,the neuronal cell bodies lost typical morphological characteristics,the degree of cytoplasmic staining was reduced,and the nuclei with deep staining were seen.The tight arrangement between the cells was lost,the gap was irregularly changed,and the necrotic neuronal cells appeared around the neurons.Compared with the PND group,the brain tissue of the Dex group showed pathological changes such as enlarged intercellular space and neuronal cell necrosis,but the degree was significantly reduced,and the pathological damage of the cerebral cortex was gradually weakened.3.TUNEL method to detect apoptosis cells in hippocampus In the PND group,apoptotic cells could be clearly seen in all parts of the hippocampus under the optical microscope,and the positive cells were apoptotic cells with green nuclei.In CG group and Sham group,only scattered apoptotic cells could be seen in the hippocampus under the microscope.Compared with Sham group,TUNEL-positive cells in the hippocampus of PND group were significantly increased.Compared with PND group,TUNEL positive cells in hippocampus of rats in Dex group were significantly reduced(P<0.05).4.Results of immunohistochemical detection of TNF-αCompared with CG group,the expression level of TNF-α in Sham group had no significant difference(P>0.05).Compared with Sham group,the expression level of TNF-α in PND group was significantly increased(P<0.05).Compared with PND group,the expression level of TNF-α in Dex group was significantly decreased(P<0.05).5.The effects of Dex on M1/M2 microglia phenotype transformation RT-qPCR method was used to detect the mRNA expression levels of iNOS,a marker of M1 microglia,and Arg-1,a marker of M2 microglia.Compared with CG group,there was no significant difference in iNOS mRNA expression level in Sham group(P>0.05).Compared with the Sham group,the mRNA expression level of iNOS in the PND group was significantly increased(P<0.05).Compared with PND group,the mRNA expression level of iNOS in Dex group was significantly decreased(P<0.05).Compared with CG group,the mRNA expression level of Arg-1 in Sham group had no significant difference(P>0.05).Compared with Sham group,the mRNA expression level of Arg-1 in PND group was significantly decreased(P<0.05).Compared with PND group,the mRNA expression level of Arg-1 in Dex group was significantly increased(P<0.05).Conclusion:Dexmedetomidine can reduce the expression of inflammatory factors by regulating the phenotypic transformation of M1/M2 microglia cells,thereby alleviating neuronal damage and improving the learning and memory function of PND model rats.Part 2 Effects of dexmedetomidine on serum inflammatory factors and perioperative neurocognitive dysfunction in elderly patients with general anesthesia Objective: To investigate the effects of dexmedetomidine on the expression of peripheral blood inflammatory factors and perioperative neurocognitive dysfunction in elderly patients with general anesthesia and the correlation between different kinds of inflammatory factors and PND.Methods: A total of 226 elderly patients with general anesthesia were selected.They were randomly divided into dexmedetomidine group(group S)and blank control group(group C).Patients in group S were injected with dexmedetomidine at 0.5μg/kg 15 min after anesthesia induction,and the infusion was completed within 15 min.It was then transfused at a rate of 0.2 μg/kg/h until 30 min before the end of surgery.Group C was injected with the same amount of normal saline at the same time and in the same way.Peripheral venous blood samples were collected 1 h before anesthesia and 24 h after anesthesia to detect TNF-α and IL-6 levels,and MMSE scores were recorded.Results: 1.During the study,76 patients were excluded because they did not meet the inclusion criteria or refused the trial,and a total of 150 patients were enrolled.There were 84 cases in dexmedetomidine group(group S)and 66 cases in blank control group(group C).2.The incidence of PND was 13.1% in group S and 24.2% in group C.The difference was statistically significant(P<0.05).3.The expressions of TNF-α and IL-6 in both groups were significantly higher than those before operation(P<0.05).Compared with group C,the expression levels of TNF-α and IL-6 in group S were significantly decreased(P<0.05).4.The expression levels of TNF-α and IL-6 were correlated with the incidence of PND,and the correlation coefficient between IL-6 and PND was R=0.598,P=0.039.The correlation coefficient between TNF-α and PND was R=0.621,P=0.035.Conclusion: There was a significant correlation between the increase of IL-6 and TNF-α and the increases of PND.Dexmedetomidine can significantly decrease IL-6 and TNF-α after surgery,which may reduce the incidence of PND in elderly patients. |
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