The Effect Of Quercetin On Db/Db Diabetic Encephalopathy Model Mice Through SIRT1/NLRP3 Pathway

ObjectiveEpidemiological studies have found that diabetes and cognitive dysfunction are closely related.Quercetin,chinese medicine monomer,has been certified with the effect on improving diabetes mellitus(DM)and cognitive impairment.However,the effect and related mechanism of quercetin on diabetic encephalopathy(DE)is still ambiguous.In this study,we used the db/db mice(diabetic model)to discover whether quercetin could improve DE through the Sirtuinl/NLRP3 pathway.MethodsThe 40 weeks age of db/db mice were randomly divided into four groups:control group,10 mice in each group(db/m,0.9%saline);model group,10 mice in each group(db/db,0.9%saline);low dosage of quercetin administration group,8 mice in each group(db/db+QL,35 mg/kg);high dosage of quercetin administration group,8 mice in each group(db/db+QH,70 mg/kg).After 12 weeks of continuous administration,we conduct behavioral tests(Morris water maze,new object recognition)related to learning and memory,glucose tolerance test(OGTT),insulin tolerance test(OGTT),samples were taken after sudden death from anesthesia.We tested blood biochemical indicators(four blood lipids)and oxidative stress indicators(SOD,MDA,CAT,GSH-PX).Nissl staining was used to detect neuronal damage.Western blot and immunofluorescence were used to detect the expression of neurotrophic factor,synapse-related proteins and SIRT1/NLRP3 pathway-related molecular proteins.ResultsBehavioral results showed that quercetin,especially in the high-dose group(70 mg/kg),improved the dysfunction of learning and memory in db/db mice.At the same time,quercetin(70mg/kg)promoted glucose and lipid metabolism,reduced the level of oxidative stress,insulin resistance and fasting blood glucose.Nissl staining results showed that the number of Nissl bodies of quercetin,especially the high-dose group(70mg/kg),was significantly increased compared with the db/db group.Western blot analysis also showed that quercetin increased the proteins expression of nerve-and synapse-related proteins(including PSD93,PSD95,BDNF and NGF)in the brain of db/db mice.Quercetin also increased the protein expression of SIRT1 and decreased the expression of NLRP3 inflammation-related proteins,including NLRP3,ASC and cleaved Caspase-1,IL-1β and IL-18).In addition,the results of the immunofluorescence experiments of SIRT1 and NGF are also consistent with the results of western blotting.ConclusionIn conclusion,the present results indicate that the SIRT1/NLRP3 pathway may be a crucial mechanism for the neuroprotective effect of quercetin against DE.