A promising impact of telmisartan on cognitive function in hypertensive rat models of Alzheimer's disease induced by beta-amyloid peptide / 中华神经医学杂志

ABSTRACT

Objective To observe the effects oftelmisartan (TEL) on learning and memory functions of animal models of Alzheimer's disease combined with hypertension.Methods Seventy male spontaneously hypertensive rats were randomly assigned into 7 groups:control group,sham-operated group,model group,low TEL group (1 mg/[kg· d]),high TEL group (10 mg/[kg· d]),low TEL+GW9662 group (Tel 1 mg/[kg·d]+GW 1 mg/[kg·d]),and high TEL+GW9662 group (Tel 10 mg/[kg·d],GW 10 mg/[kg·d],n=10);the lateral cerebral ventricle of rats in the later 5 groups were injected with beta-amyloid peptide 1-42 (Aβ1-42);rats in the sham-operated group were given the same volume of normal saline,and those in the control group did not give any treatment.The learning and memory abilities of these rats were detected by Morris Maze test;microglia level and casepase-3 expression were assessed by immunohistochemical stainning.Results Constant-bearing navigation indicated that as compared with the model group,the high TEL+GW9662 group,control group and sham-operated group had significantly shorten escape latency on the 3rd d of experiment (P＜0.05),and as compared with the model group,the low TEL group,high TEL group and high TEL+GW9662 group had significantly shorten latency (P＜0.05).Spatial probe test showed that the times of crossing the platform,target quadrant residence time in the low TEL group,high TEL group and high TEL+GW9662 group were significantly larger/longer than those in the model group (P＜0.05).The casepase-3 expression and microglia level in the CA1 area of model group were significantly higher than those in the control group (P＜0.05);The Ibal and caspase-3 expressions in the low TEL group,high TEL group and high TEL+GW9662 group were significantly weaker than those in the model group (P＜0.05).Conclusion TEL has preventive effect on cognitive decline in rat models of Alzheimer's disease complicated with hypertension,and can be restrained by GW9662,which suggests that these benefits might be partly resulted from PPAR-γ activation and intracranial infection inhibitation.