A Promising Impact Of Telmisartan On An Animal Model Of Alzheimer’s Disease By Lateral Ventricle Aβ1-42 Injection Combined With Hypertension

Background and ObjectiveAlzheimer’s disease is a kind of a nervous system degenerative disease,characterized by progressive cognitive decline, irreversible cognitive impairment, etc.;Along with the aging society, the incidence of hypertension also increased year by year, the two concurrent increasingly common in the elderly, treatment and nurse bring heavy burden to family and society. But at the moment for the composite condition of clinical use comprehensive treatment, more alleviate disease progression,but poor curative effect. To optimize the drug, and pioneering ideas, set up a kind of alzheimer’s disease combined composite animal model of hypertension to observe the effects of telmisartan and the possible mechanism of telmisartan on an animal model of Alzheimer’s disease combined with hypertension.Methods8 weeks Spontaneously Hypertensive Rats(SHR) were randomly assigined to 7groups: control group(n=10);sham group(n=10);model group(n=10); telmisartan :low group(1mg.kg-1.d-1,n=10);high group(10mg.kg-1.d-1,n=10);telmisartan+GW9662: low group(TEL 1mg.kg-1.d-1+GW 1 mg.kg-1.d-1,n=10),high group(TEL 10 mg.kg-1.d-1,GW10 mg.kg-1.d-1,n=10);model group and treatment groups rats’ lateral cerebral ventricle were injected by Aβ1-42 via Animal brain stereotaxic instrument. 4 weeks postoperative,Cognitive function were tested by Morris Maze and Systolic blood pressure were recorded,cerebral cortex and hippocampus CA1 area were dyed by immunohistochemical to detect neurons Inflammation, apoptosis.Results1.Compared with control group and Model group,TEL(high) and TEL+GW(high)groups showed a significant reduction in systolic blood pressure(p<0.05).2.Compared with the model group,TEL( low),TEL +GW(low) and TEL+GW(high) groups had a lower escape latency,the percent of time in target quadrant was higher(p<0.05),while TEL+GW(low) showed no difference with the model group.(p>0.05).3.Compared with the crotrol group, the number of the Iba1 positive cells in hippocampus CA1 area, the expression of TNF-α,IL-1,IL-6,Caspase-3,Bcl-2showed a statistical increase(p<0.05);Compared with the model group,a significant increase were observed in the expression in the number of the Iba1 positive cells, the expression of TNF-α,IL-1,IL-6,Caspase-3,as well as a significant reduction in Bcl-2in group of TEL(low),TEL+GW(low) and(high).ConclusionLow dose telmisartan has a preventive effect on the cognitive decline in this Alzheimer disease acomplicated with hypertension mouse model,which could be restrained by GW9662,suggests its partly because of the activation of PPAR-γ, which Inhibit inflammation,reduce the apoptosis and rotect the neurons;in addition,a high dose of telmisartan also has a steady blood presure,which may intensify this effection.