The Role Of The ACE And AGTR In The Hippocampus Of AD Rats And Effect Of Perindopril And Valsartan

OBJECTIVES: To determine the learning and memory ability and the morphous, explore the role of angiotensin converting enzyme (ACE), two subtypes of angiotensin II receptor (AGTR) that is AGTR1 and AGTR2 in the hippocampus of alzheimer disease (AD) model rats, and to approachthe effect of perindopril - angiotensin converting enzyme inhibitor (ACEI) and valsartan -angiotensin II receptor blocker (ARB) on AD.METHODS: Eighty healthy female Sprague-Dawley (SD) rats were selected and then devided into four groups randomly, that is the control group, the AD group, the perindopril group, and the valsartan group.The AD model was set up by injection withβ-amyloid 1-42( Aβ1-42) into the right hippocampus stereotacticly. Learning and memory functions were tested by Y-type electric maze; The number of abnornmal neurons was determined by HE staining, the deposition of amyloid was measured by Cango red staining, expression level of the ACE was estimated by spectrophotometry, and both of AGTR1 and AGTR2 were observed by immunohistochemistry (IH).RESULTS:1. the behavior of rats after the surgeryIt shows that rats of the AD group need more time to escape from the electrical stimuli (P=0.000). Both the perindopril group and the valsartan group need more time to escape than the AD group (both P=0.000). There is no significant difference between the perindopril group, the valsartan group and the control group (all P>0.05).2. HE stainingThere were more normal neurons in the region of CAl in the control group than in the AD model group. The neurons showed regular arrangement, with distinct edges and clear and obvious nucleus and nucleolus. No significant necroses of pyramidal neurons were found. In the AD group, normal neurons in the region of CAl decreased greatly, the neurons had irregular arrangement, and the edge of many cells was unclear. The nucleus and nucleolus of many neurons became ambiguous; The neurons is less dense than the control group (P=0.000). Both the perindopril group and the valsartan group showed some neurons necrosed; The neurons is more dense than the AD group for both of them (P=0.000).3. Congo red stainingDeposition of positive staining substance around which neurons shrank and had irregular arrangement was found in the AD group. No deposition of such substance can be found in the other 3 groups.4. Change of ACE activityActivity of ACE the AD group is higher than the control group and the perindopril group(P=0.003, 0.005 respectively).5. Expression of AGTRlOptical density (OD) value of the AD group is higher than the control group (P=0.000),and the valsartan group (P=0.001).6. Expression of AGTR2Optical density (OD) value of the AD group is higher than the control group (P=0.000),and lower than the valsartan group (P=0.005).CONCLUSIONS:1. The activity of ACE increased in the AD rats. Perindopril can prolong the development of AD.2. AGTRl can promote the development of AD and its role can be inhibited by valsartan.3. AGTR2 can prolong the development of AD.