Study on the mechanism of brain insulin resistance in diabetic encephalopathy and Alzhei-mer's disease by"homotherapy for heteropathy"with Dihuang Yinzi
Objective We observed the therapeutic effects of Dihuang Yinzi on db/db mice and APP/PS1 mice,and investigated the molecular mechanism of Dihuang Yinzi to improve the brain insulin resistance in diabetic encephalopathy(DE)and Alzheimer's disease(AD)by the"homotherapy for heteropathy".Methods In this study,we set up the DE disease model group and the AD disease model group,respectively.In the DE disease model group,10 db/m mice were used as a blank control group(db/m group),and 30 db/db mice were randomly divided into the model group(db/db group),the Dihuang Yinzi group(db/db+DHYZ group,30.03 g/kg),the metformin group(db/db+MET group,0.61 g/kg).In the AD disease model group,10 wild-type C57BL/6J mice were used as a blank control group(C57 group),and 30 APP/PS1 mice were randomly divided into a model group(APP/PS1 group),a Dihuang Yinzi treatment group(APP/PS1+DHYZ group,30.03 g/kg),and a memantine treatment group(APP/PS1+MEM group,6.1 mg/kg).After 4 weeks of drug intervention,mice hippocampus glucose and in-sulin levels were measured by glucose oxidase assay and enzyme-linked immunosorbent assay(ELISA),respectively;his-topathological changes in mice hippocampus were observed by hematoxylin-eosin(HE)staining;and hippocampus phos-phoinositide 3-kinase(PI3K),protein kinase B(Akt1),and phospho-protein kinase B(pAkt1)in hippocampus tissues was detected by Western blot.Immunohistochemistry was used to detect the expression of insulin receptor substrate 1(IRS1),glucose transporter 4(GLUT4)in hippocampus tissues.Results The hippocampus of db/db mice and APP/PS1 mice showed pathologi-cal changes such as disorganization of neuronal arrangement,significant reduction of cell number;glucose content was elevated in both mice(P＜0.05);hippocampus insulin was elevated in db/db mice(P＜0.01)and decreased in APP/PS1 mice(P＜0.01);the protein expressions of PI3K,pAkt1/Akt1,GLUT4 were increased in both mice(P＜0.01),and IRS1 protein expression was significantly elevated(P＜0.01).After the intervention of Dihuang Yinzi,the hippocampus pathological changes in db/db mice and APP/PS1 mice were reduced and the cell number increased;the glucose content was reduced in both mice(P＜0.05);the hippocampus insulin was reduced in db/db mice(P＜0.01)and increased in APP/PS1 mice(P＜0.05);and the protein expression of PI3K,pAkt1/Akt1,and GLUT4 was elevated(P＜0.05,P＜0.01)and IRS1 protein expression decreased(P＜0.05,P＜0.01).Conclusion Dihuang Yinzi can reduce the insulin resistance of DE and AD brains by regula-ting the insulin-related IRS1/PI3K/Akt/GLUT4 signaling pathway,thus exerting the effect of"homotherapy for heteropathy"on both of them.
Diabetic encephalopathyAlzheimer's diseaseHomotherapy for heteropathyInsulin resistanceDihuang Yinzi
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