Effect Of Flurbiprofen Axetil On Early Cognitive Function In Sd Rats After Burns And Its Mechanism

Research Background:Burns are devastating injuries that often lead to high morbidity,depressed mood,and a reduced quality of life.In addition to immediate intensive care,burns often require long-term treatment,multiple outpatient visits(dressing change,etc.),and multiple reconstructive surgery and hospitalizations.These burn-related health consequences often place additional socioeconomic burdens on the victims and their families.Thermal damage promotes tissue inflammation and pain,which is difficult to control.Studies have shown that anesthesia and analgesia can affect the results of burn models in rats.Different peripheral mechanisms appear to be related to burn pain,but further research is needed.Substantial preclinical and some retrospective clinical evidence suggests that anesthesia may impair cognitive ability.Increasing evidence from preclinical studies indicates that anesthetics are powerful modulators of neuronal development and function that may cause deleterious effects.The purpose of this study was to investigate whether flurbiprofen axetil is sufficient to reduce the pain and inflammation caused by burns and its effect on early cognition,and to elucidate the molecular mechanism of flurbiprofen axetil in treating thermal injury models in rats and reducing early cognitive dysfunctionObjective:Postoperative delirium(POD)is common postoperative complication in elderly patients.The incidence of POD was found to be 3.6%-28.3%in elderly patients after noncardiac surgery.Theoretically,flurbiprofen axetil can reduce the pain and reduce the occurrence of cognitive impairment by inhibiting the local inflammation of the burn and the inflammation of the central nervous system.Therefore,the purpose of this study was to study the effects of flurbiprofen axetil on early cognitive function in SD rats after burns,and to explore its possible mechanism to provide a reliable experimental basis for the prevention and treatment of postoperative cognitive impairment in clinical burn patients.Experiment 1:Effect of Flurbiprofen Axetil on Early Cognition andInflammation in Burned RatsMethods:The rat burn model was constructed,and the success of the model was determined by HE staining.The experimental groups were:1)Normal control group(Control);2)Burn model group(Model);3)Low-dose treatment group(5 mg/kg);4)Medium-dose treatment group(10 mg/kg);5)High-dose treatment group(15 mg/kg).Rats in each group(n=6)were treated according to the above groups,and the normal control group was not treated with burns.The flurbiprofen axetil was administered 30 minutes before modeling and 24 hours after modeling,and the rats were sacrificed 3 days later.Electric Von Fray fibre was used to test the mechanical pain threshold of the rats on 12,24,36,48,60 and 72 hours post-injury respectively.Morris water maze was used to observe the spatial memory and learning ability of the rats.HE staining was used to detect the pathological results of skin and hippocampus in each group.The expression levels of TNF-α,CINC-1,IL-6 and IL-1β in serum of each group were detected by ELISA.TUNEL was used to detect the apoptosis level of hippocampal cells in each group.Results:Model was built successfully.After being treated with flurbiprofen axetil,the epidermal layer of tissues in the stagnation zone of the treatment group rats became thinner,and the swelling of the dermis,the change of collagen structure,the infiltration of local inflammation,the destruction of tissue and other injuries tend to be alleviated.This effect becomes more pronounced as the dose of the drug increases.After being treated with flurbiprofen axetil,the mechanical pain threshold of the treatment group rats was significantly increased compared with the model group(P<0.05),but there was no significant difference between the treatment groups.The Morris water maze experiment results showed that burn injury reduced the spatial memory and learning ability of the rats.After being treated with flurbiprofen axetil,the spatial memory and learning ability of the rats were improved,and the hippocampal pathological changes were also improved compared with the model group,but the differences between the flurbiprofen axetil treatment groups were not significant.Compared with the normal control group,the levels of TNF-α,CINC-1,IL-6 and IL-1β in the model group were significantly increased(P<0.05),and the rat hippocampal cells apoptosis was also significantly increased(P<0.05).Compared with the model group,the levels of TNF-α,CINC-1,IL-6 and IL-1β in the flurbiprofen axetil treatment groups were significantly reduced(P<0.05),and the apoptosis of hippocampal cells was also significantly reduced(P<0.05)with the most obvious reduction in the high-dose group.Conclusion:After being treated with flurbiprofen axetil,the expressions of inflammatory factors such as TNF-α,CINC-1,IL-6 and IL-1β were inhibited,which relieves pain hyperalgesia and alleviates early cognitive dysfunction in rats.Experiment 2:Molecular Mechanisms of Flurbiprofen Axetil on Early Cognition in Burned RatsMethods:The rat burn model was constructed,and the success of the modeling was determined by HE staining.The experimental groups were:1)Normal control group(Control);2)Burn model group(Model);3)Low-dose treatment group(5 mg/kg);4)Medium-dose treatment group(10 mg/kg);5)High-dose treatment group(15 mg/kg).Rats in each group(n=6)were treated according to the above groups,and the normal control group was not treated with burns.Flurbiprofen axetil was administered 30 minutes before modeling and 24 hours after modeling.Based on the results of the mechanical pain threshold in Experiment 1,rats in each group were sacrificed 48 hours after modeling.The pathological results of skin and hippocampus were detected by HE staining.The mRNA expression levels of BDNF,Caspase3,GFAP and MMP9 in the hippocampus of each group rats were detected by qPCR.The expression and localization of BDNF in each group were detected by immunohistochemical staining.Western blot was used to detect the expression levels of BDNF,Caspase3,p38 and p-p38 protein in each group.Results:Compared with the normal control group,the mRNA expression levels of BDNF,Caspase3,GFAP and MMP9 in the hippocampus of the model group were significantly increased,and the protein expression levels of BDNF,caspase3 and p-p38 were also significantly increased,The differences were statistically significant(P<0.05).Compared with the model group,the mRNA expression levels of BDNF,Caspase3,GFAP and MMP9 in hippocampus of each flurbiprofen axetil treatment group were significantly reduced,and the protein expression levels of BDNF,caspase3 and p-p38 were significantly decreased.The differences were statistically significant(P<0.05),but the differences between the flurbiprofen axetil treatment groups were not significant.Conclusion:Treatment with flurbiprofen axetil inhibits the mRNA expression levels of BDNF,Caspase3,GFAP and MMP9 and the protein expression levels of BDNF,caspase3 and p-p38 via the p38 signaling pathway,which reduces early cognitive dysfunction of the SD rats after burns.