| Objective:With aging problem has become more and more serious,the incidences of Alzheimer’s disease(AD)and diabetes increase dramatically and bring great distress to the modern society and families.The prevention and cure of AD and diabetes have become major public health concern.The incidence of AD increases with aging,and researches show that diabetes mellitus is a great risk factor that contributes to AD.Neurofibrillary tangle,composed of hyperphosphorylated tau protein,is one of the typical pathological features in the brains of AD patients.Modern research found that Puerarin can protect islet beta cells in T2 DM rat.It is reported that Puerarin can also protect the hippocampal neurons from injuries and can alleviate cognitive deficits in AD mice.The present study is to study the effects of Puerarin on the level of tau phosphorylation in the brains of AD and type 2 diabetes mellitus animal models,and to explore the underlying mechanisms.Our study can provide experimental data and theoretical foundation for clinical application of Puerarin to treat AD and diabetic cognitive dysfunction.Methods:1.To investigate the effect of Puerarin on the level of tau phosphorylation in the olfactory bulb of AD model rat brains,male SD rats were randomly divided into three groups: Normal control group(control group),AD model group(model group),Puerarin group(Pue group,80 mg/kg per day).D-galactose(160 mg/kg per day)was injected intraperitoneally for 6 weeks to reproduce AD-like pathologies in rat brain.The level of tau-1,pS396,tau-5 and the level of tGSK-3β and pSGSK-3β in the olfactory bulb was detected by Western blot.In order to further examine the dose effect of Puerarin on the level of tau phosphorylation,male SD rats were randomly divided into 4 groups: each group received intraperitoneal in jection of D-galactose(160 mg/kg per day)for 6 weeks and treated with Puerarin at 0,40 mg/kg per d,80 mg/kg per d or 160 mg/kg per d separately.The level of tau-1,pS396 in the olfactory bulb was detected by Western blot.2.To investigate the effect of Puerarin on the level of tau phosphorylation in T2 DM rat brains,male SD rats were first randomly divided into model group and control group.Rats in the model group were fed with high fat diet for 4 weeks and then injected intraperitoneally with STZ(30mg/kg)for once.After successful modeling,T2 DM rats were randomly divided into T2 DM group(model group),Puerarin group(80mg/kg per d)(Pue group)and rosiglitazone group(RSG group).During the treatment,we measured the body weight,blood glucose level once a week and check the food intake and drinking water daily.After 4 weeks of treatment,we used HE staining to observe the tissue structure of rat islets,detected the expression of tau-1、PS396、tau-5、OGA and OGT by Western blot in the hippocampus of rat brain,and used immunohistochemical method to observe the expression and distribution of tau-1 and PS396 in the CA1 area,CA3 area and dentate gyrus(DG)of hippocampus in rat brain.Results:1.Puerarin significantly reduced the level of tau phosphory-lation in the olfactory bulb of AD model rats.2.All three dosages of Puerarin can effectively reduce the level of tau phosphorylation in the olfactory bulb of AD model rats(P<0.01),but the effect was not shown to be dose-dependent.3.Compared with the control group,the activity of GSK-3β in the olfactory bulb of AD model rats was significantly higher(P<0.01),and Puerarin could effectively reduce the level of GSK-3β activity induced by D-galactose(P<0.05).4.Compared with the normal group,the weight of rats in the model group was decreased significantly(P<0.01)whlie Puerarin treatment could effectively increase the body weight of T2 DM rats(P<0.01).5.Puerarin can effectively reduce the level of fasting blood glucose(P<0.05)in T2 DM model rats.6.Puerarin can effectively improve the intake and drinking water of T2 DM model rats(P<0.01).7.Compared with the normal group,the pancreatic islet struc-ture was destroyed obviously,the morphology was irregular,the area and the number of islets were significantly reduced,the cyto-plasm of islet cells was reduced,and some of the cells showed vacuolar degeneration.Puerarin administration can significantly improve the impairments of islet structure in model rats.8.Compared with the normal group,the expression of Tau-5 in hippocampus of model group was increased significantly(P<0.01)and the level of Tau-1 was decreased obvioulsy(P<0.05).Puerarin treatment could not ameliorate the increased level of total tau protein and tau phosphorylation in the hippocampus of T2 DM rat brain.9.Compared with the control group,the level of OGT in hippo-campus of model group was decreased obviously(P<0.05),and there was no significant difference in OGA between the control and T2 DM model group.Puerarin treatment failed to alleviate the decreased level of OGT in the hippocampus of T2 DM rat brain.Conclusion:1.Puerarin can effectively reduce the increased tau phosphory-lation in the olfactory bulb of young rats induced by D-galactose,and the GSK-3β pathway may be involved in the effects of Puerarin on tau phosphorylation in AD rat brain.2.Puerarin can reduce the level fasting blood glucose,incr-ease the body weight of rats,and reduce the intake of food and drinking water of T2 DM rats.3.Puerarin treatment could not rescue the increased tau phos-phorylation and down-regulated glycosylation in the hippocampus of T2 DM rats. |
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