Abstract: BACKGROUND: Studies have shown that angiotensin-converting enzyme inhibitor (ACEI), an antihypertensive drug, can reduce the production of reactive oxygen species, resist oxidative stress, reduce neuronal apoptosis, and thereby alleviate the procession of Alzheimer’s disease.
OBJECTIVE: To explore the effect and mechanism by which ACEI antihypertensive drugs improve learning and memory impairment after Alzheimer’s disease. 
METHODS: Firstly, 48 Sprague-Dawley rats were randomly divided into control group, model group, captopril group and donepezil hydrochloride group, 12 in each group. Secondly, rat models of Alzheimer’s disease by injected with beta-amyloid 1-42 were established except the control group injected with normal saline. Then, we offered different intervention treatments for each group and observed the general condition at 2 weeks after intervention. After modeling, the control and model groups were intragastrically given the same amount of normal saline per day; the captopril group was given 2.5 mg/kg captopril; the donepezil hydrochloride group was given 1.0 mg/kg donepezil hydrochloride. Thirdly, the Morris water maze was used to carry out directional navigation and space exploration experiments in rats, in order to explore the effects of captopril on learning and memory impairment in the rat model. In the end, the content of reactive oxygen species in the rat hippocampus was investigated by fluorescence spectrophotometry, and the expression of 8-hydroxy-2’-deoxyguanosine and insulin degrading enzyme in the hippocampus was detected by immunohistochemistry. The study protocol was approved by the Ethics Committee of Jiamusi University. 
RESULTS AND CONCLUSION: Subjective observation showed that the spirit of rats in the model group was significantly depressed and the diet was reduced after modeling; and there were no significant changes in the other three groups. For the Morris water maze test, compared with the control group, the average escape latency and swimming distance were significantly increased in the model group, while the fourth quadrant dwell time and swimming distance percentage were significantly reduced (P < 0.01). Compared with the model group, the average escape latency and swimming distance of captopril group and donepezil hydrochloride group were significantly reduced, while the fourth quadrant dwell time and swimming distance percentage were significantly increased (P < 0.01). However, there were no significant difference between the captopril group and donepezil hydrochloride group (P > 0.05). Compared with the control group, the levels of reactive oxygen species and 8-hydroxy-2’-deoxyguanosine were significantly increased in the model group, and the expression of insulin degrading enzyme was significantly reduced (P < 0.01). Compared with the model group, the levels of reactive oxygen species and 8-hydroxy-2’-deoxyguanosine were significantly reduced in the captopril group and donepezil hydrochloride group, and the expression of insulin degrading enzyme was significantly increased (P < 0.01). There was no significant difference between the captopril group and donepezil hydrochloride group. In conclusion, captopril can improve learning and memory impairment in Alzheimer’s disease rat models induced by beta-amyloid 1-42, and our findings also suggest the potentially beneficial effects of certain renin angiotensin aldosterone system activation in high-risk Alzheimer’s disease populations. 

Key words: beta-amyloid 1-42, Sprague-Dawley rat, reactive oxygen species, 8-hydroxy-2’-deoxyguanosine, insulin degrading enzyme, Alzheimer’s disease