Salidroside Improves Cognitive Dysfunction In Diabetes Mice Through CXCR4/TXNIP Pathway

ObjectiveFirstly,we will explore the role of CXCR4/TXNIP pathway in cognitive impairment in diabetic mice,and secondly,we will investigate whether salidroside can improve cognitive impairment in diabetic encephalopathy mice by modulating CXCR4/TXNIP pathway.MethodsAdult male C57BL/6 mice were randomly divided into four groups: control group(CON group),diabetes group(DM group),salidroside group(SAL group),salidroside+CXCR4 specific inhibitor(AMD3100 group),with 10 mice in each group.Except CON group,the remaining three groups were intraperitoneally injected with streptozotocin(150mg/kg)to establish diabetes mouse models.SAL+AMD3100 group and SAL group were treated with SAL(150mg/kg)by gavage,and CON group was treated with the same dose of normal saline;Once a day for 12 consecutive weeks;During intragastric administration,the body weight changes of mice in each group were detected weekly and fasting blood glucose was monitored and recorded.In SAL+AMD3100 group,AMD3100 was injected intraperitoneally,twice a week,with a dose of 5 mg/kg.After 12 weeks,Morris water maze(MWM)was performed to test the learning and memory abilities of mice in each group.The number of neurons was measured by Nissl staining.Immunofluorescence staining(IF)was used to detect the expression of CXCR4 and TXNIP proteins.Detection of CXCR4,TXNIP,NLRP3,GSDMD,Caspase-1,IL-1 by immunoblotting β Protein expression.ResultsCompared with CON group,DM group had higher blood glucose and lower body weight.The water maze results showed that the swimming track was prolonged,the escape latency was prolonged,the time in the target quadrant where the platform was located was significantly reduced,and the number of crossings was reduced(P<0.05).The results of Nissl staining showed that there were obvious cell structure destruction,irregular morphology of Nissl corpuscles,decreased number and cell hypertrophy in the CA1 area of mouse hippocampus;The difference was statistically significant(P<0.01).The results of immunofluorescence assay showed that the expression of CXCR4 and TXNIP in DM group increased significantly(P<0.01).Western blot showed that DM group CXCR4,TXNIP,NLRP3,GSDMD,IL-1 β.The relative expression increased significantly(P<0.01).Compared with DM group,the blood glucose in SAL group decreased.The water maze results showed that the swimming track was shortened,the escape latency was shortened,the time in the target quadrant where the platform was located was significantly prolonged,and the number of crossings was increased(P<0.05).The results of Nissl staining showed that the number of Nissl corpuscles in the CA1 area of the mouse hippocampus increased,the cell morphology and structure were relatively complete,and the cells were arranged closely and regularly.The results of immunofluorescence assay showed that the expression of CXCR4 and TXNIP in SAL group decreased significantly(P<0.01).Western blot test results showed that SAL group CXCR4,TXNIP,NLRP3,GSDMD,IL-1 β.The relative expression decreased significantly(P<0.05).The results of water maze showed that compared with SAL group,the swimming track of SAL+AMD3100 group was prolonged,the escape latency was prolonged,the time in the target quadrant where the platform was located was significantly reduced,and the number of crossings was reduced(P<0.05).The results of Nissl staining showed that the morphology of Nissl corpuscles was irregular,the number of Nissl corpuscles was decreased,the cells were hypertrophic,and there were vacuoles in the CA1 area of mouse hippocampus;The difference was statistically significant(P<0.01).The results of immunofluorescence assay showed that the expression of CXCR4 and TXNIP in SAL+AMD3100 group increased significantly(P<0.01).Western blot showed that CXCR4,TXNIP,NLRP3,GSDMD,IL-1β in SAL+AMD3100 group The relative expression increased significantly(P<0.01).ConclusionsSalidroside can improve neuroinflammation and reduce hippocampal neuronal scorch in diabetes mice.The mechanism may be related to CXCR4/TXNIP.