| Objective: Combination the method of pharmacology and gene regulation,curcumin and mi R-455 were used to treat the cell and mouse model of Alzheimer’s disease to explore whether they can synergistically inhibit histone deacetylase 2 to improve the pathology of Alzheimer’s disease.We also explore whether they can synergistically improve the cognitive function in Alzheimer’s disease mouse model.Method: By searching the Targetscan database for microRNAs which can combine with the 3’UTR of HDAC2,then we perform q PCR to test the expression of microRNAs in AD cell model compared with SH-SY5 Y cells.Then we confirmed whether mi R-455 can combine with the 3’UTR of HDAC2 by luciferase reporter assay.In SH-SY5 Y cell that overexpressing APP(APPswe695 cell line),we treated the cell with either curcumin or transfected mi R-455 mimic or at the same time to confirm whether they can synergistically inhibit HDAC2 to improve the pathology of Alzheimer’s disease.APP/PS1 mice were divided into four groups randomly: Ctrl(150mg/kg·d saline+ Lentimi R-NC,n=5),Cur(150mg/kg·d curcumin+ Lenti-mi R-NC 2μl,n=5),mi R-455(150mg/kd·d saline+ Lenti-mi R-455 2μl,n=5),Cur+mi R-455(150mg/kd·d curcumin+ Lenti-mi R-455 2μl,n=5),water maze was used to test the cognitive function of the mice.Western blot were used to test the pathology of Alzheimer’s disease.Results: We searched the Targetscan database and determined that mi R-455 can combine with the 3’UTR of HDAC2.Compared with the control group,the expression of mi R-455 is lower in APPswe695 cells.By luciferase activity assay,it is indicated that mi R-455 can combine with the 3’UTR of HDAC2 and suppressed the expression of HDAC2.We also found that curcumin can suppress the expression of HDAC2 and improve the pathology of Alzheimer’s disease.To verifity whether they can synergistically suppress the pathology of AD,mi R-455 and curcumin was administrated at the same time to treat the AD mouse model.The results indicated that mi R-455 and curcumin can synergistically suppress the expression of HDAC2 and the pathology of AD.In APP/PS1 mice experiment,we found that treat the mice with mi R-455 and curcumin at the same time,they can synergistically improve the cognitive function of the APP/PS1 mice.By western blot,we found that mi R-455 and curcumin can synergistically suppress the expression of HDAC2 and the pathology of AD.Conclusion: The results indicated that curcumin and mi R-455 can improve AD pathological and cognitive function in the AD mouse model.A combination of pharmacology and gene regulation may be a potentially effective treatment for AD. |
