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BACKGROUND: Chronic cerebral hypoxia and ischemia have been shown to be related to occur-rence of sporadic Alzheimer’s disease,and βand γ-secretase play an important role in the gen-eration of β-amyloid protein.Early clinical symptoms in Alzheimer’s disease patients include learn-ing and memory deficits.OBJECTIVE: To measure learning and memory,as well as βand γ-secretase activities in the hippocampus of a cerebral ischemia/hypoxia rat model with chronic cerebral hypoperfusion.DESIGN,TIME AND SETTING: A randomized,controlled,animal experiment was performed at the Department of Pathology,Capital Medical University from March to December,2008.MATERIALS: βand γ-secretase activity kits were purchased from R & D Systems,USA.METHODS: Male Sprague Dawley rats,aged 23 weeks,were randomly assigned to model (n = 56) and sham-surgery (n = 46) groups.Cerebral hypoperfusion rat models were established by bilateral common carotid occlusion.MAIN OUTCOME MEASURES: Morris water maze was used to test changes in escape latency and path length,and βand γ-secretase activities were measured on days 10,30,90,and 180 following surgery.RESULTS: Progressive cognitive impairment resulted from 30 days of chronic cerebral hypoperfu-sion,which lasted for 180 days after cerebral hypoperfusion.β-secretase activity was increased at 10 days after hypoperfusion,which continued until 180 days,with a 14.25% increase compared to the sham-surgery group;γ-secretase activity was increased by 10.5%.CONCLUSION: Chronic cerebral hypoperfusion results in impaired spatial memory and upregu-lated βand γ-secretase activities,which could play an important role in β-amyloid production.
BACKGROUND: Chronic cerebral hypoxia and ischemia have been shown to be related to occur-rence of sporadic Alzheimer’s disease, and βand γ-secretase play an important role in the gen-eration of β-amyloid protein. Early clinical symptoms in Alzheimer’s disease patients include learn-ing and memory deficits. OBJECTIVE: To measure learning and memory, as well as β and γ-secretase activities in the hippocampus of a cerebral ischemia / hypoxia rat model with chronic cerebral hypoperfusion. DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed at the Department of Pathology, Capital Medical University from March to December, 2008. SPECIALS: βand γ-secretase activity kits were purchased from R & D Systems, USA. METHODS: Male Sprague Dawley rats, aged 23 weeks, were randomly assigned to model (n = 56) and sham-surgery (n = 46) groups. Cerebral hypoperfusion rat models were established by bilateral common carotid occlusion. MAIN OUTCOME MEASURES: Morris water maze was used to test changes in escape latency and path length, and βand γ-secretase activities were measured on days 10, 30, 90, and 180 following surgery. RESULTS: Progressive cognitive impairment resulted from 30 days of chronic cerebral hypoperfu- sion, which lasted for 180 days after cerebral hypoperfusion .β-secretase activity was increased at 10 days after hypoperfusion, which continued until 180 days, with a 14.25% increase compared to the sham-surgery group; γ-secretase activity was increased by 10.5% .CONCLUSION: Chronic cerebral hypoperfusion results in impaired spatial memory and upregu-lated βand γ-secretase activities, which could play an important role in β-amyloid production.