Captopril And Losartan On Vascular Dementia In Rats And Its Mechanism

Abstract:Objective:each observation of rennin-angiotensin system inhibitor captopril and Losartan on the model of vascular dementia (VD) improvement of learning and memory of rats and effect of treatment, and preliminary discussion on its mechanism of action. Method: function of learning and memory in Morris water maze filter60normal male SD rats; randomly assigned to operations group (48) and sham operation group (12); operation group at different time points, respectively, permanent ligation of the left and right carotid artery in rats established by VD model.4weeks after the surgery, screening model for successful rat36, randomly divided into2.5mg/kg captopril group,2.0mg/kg losartan group and model group, only12per group.The medication group daily1time fills the stomach to the medicine, the model group and the sham-operation group gives and so on the capacity physiological saline, continual4weeks.4weeks after the drug, Morris water maze test groups of rats learning and memory abilities.Some rats with4%formaldehyde perfusion fixed, paraffinembedded brain tissue, consecutive coronal sections, HE staining and immunohistochemical staining (SABC method), TUNEL assay apoptosis of hippocampal neurons by light microscopy to observe the damage of hippocampal neurons, Bcl-2and Bax protein expression and hippocampal neuron apoptosis.GD-10.0multimedia color pathological analysis system analysis of Bcl-2and Bax positive expre-ssion of the average gray value, the higher the gray value, the more expression products. Some rats were decapitated brain, separation of the cortex and hippocampus, ice homogenate,3000r/min speed centrifugal10min preparation of tissue homogenate.Measured by radioimmunoassay the cerebral cortex and hippocampus tissues TNF-a, IL-1βcontent; Hydroxylamine method for the determination of the cerebral cortex and hippocampus in the Super oxides differences of enzyme (SOD) activity; Thiobarbituric acid (TBA) determination in cerebral cortex and hippo-campus of malondialdehyde (MDA) content; Determination of nitrate reductase in cerebral cortex and hippocampus of nitric oxide (NO) content; Chemical colorimetric method for the determination in cerebral cortex and hippocampus tissues of nitric oxide synthase (NOS) and cholinesterase (AChE) activity.Abdominal aorta takes blood, Hemorheology automatic as soon as blood flow changes measured was measured. Results:(1)4weeks after surgery:①navigation test:With the increase in the number of training, the rats in each group the average escape latency were short-ened. Compared with the sham group, the operated rats escape latency were significantly prolonged (p<0.05).②spatial probe test:compared with the sham group, model group in the120s through the platform signifi-cantly fewer (p<0.05).(2)4weeks after the drug:①navigation test: after5days of water maze training, rats escape latency, captopril and losartan treatment group compared with model group was significantly shorter (p<0.05);②spatial probe test:120s across the platform number of captopril and losartan treatment group compared with model group were significantly increased (p<0.05).(3) pathological (HE dyed): sham operation group of neurons in the hippocampus of neat and tidy, form full cell number, cells have normal, larger, nuclear centers, big and round, and light blue, clear nucleolus nuclear envelope, nucleoli dyed purple, cytoplasmic colored light and even. Model rats hippocampus neurons arranged in disorder, reduce the number of nucleus pyknosis stain. Each treatment group can improve the above-mentioned neuronal damage.(4) TUNEL assay:the sham group rat hippocampus can be seen a small number of cell nuclei were brown, the hippocampus of model rats cell nucleus into a brown, uneven, and showed a RING finger-like structure, with the sham group In comparison, the positive rate of apoptotic cells was significantly enhanced (p<0.05). Captopril and losartan in the treat-ment group, hippocampus, nucleus into brown cells were significantly reduced, the positive rate of apoptotic cells was significantly lower (p <0.05).(5) immunohistochemistry:each rat hippocampal Bcl-2, Bax positive neurons staining are cytoplasmic brownyellow material deposited on the main, some membrane and nuclear membrane coloring and can display the neurons contour. Hippocampus of rats, sham operation group, Bcl-2, Bax showed a small amount of expression. Model rats, Bcl-2and Bax protein expression was significantly increased compared with the sham group was significant (p<0.05). The captopril group and losartan group Bcl-2and Bax protein expression to a significant improvement (p <0.05).(6) cortical and hippocampal tissue homogenates:the captopril group and the losartan treatment group the cerebral cortex and hippo-campus SOD activity compared with the model group was significantly increased (p<0.05), compared with the model of the two treatment groups in the cerebral cortex and hippocampus MDA content group was signi-ficantly lower (p<0.05). Captopril group and the losartan treatment group the cerebral cortex and hippocampus the the NOS vitality, and NO content compared with the model group was significantly lower (p<0.05). Capto-pril and losartan treatment group on the cerebral cortex and hippocampus of TNF-acontent and IL-1βcontent than in model group decreased signi-ficantly (p<0.05). Compared with the model group, captopril and Losartan in the treatment group reduces AChE activity of hippocampus in rats (P<0.05).(7)Hemorheology:Compared with model group in the captopril group and losartan group whole blood low viscosity cutting, the cutting and plasma viscosity was significantly decreased (p<0.05).Conclusion:(1) At different time points, respectively, permanent ligation of the left and right common carotid artery was successfully prepared VD model;(2)Captopril and losartan can improve VD model of learning and memory in rats, reduce hippocampal neuronal damage. Its mechanisms and related to the following factors:①May affect the expression of Bcl-2and Bax protein expression, to reduce the apoptosis of hippocampal neurons.②Inhibition of AChE activity in brain tissue, reducing degradation of ACh-related;③Enhanced with increased SOD activity oxygen free radical scavenging, reducing NOS activity, reducing the NO content, reducing oxygen free radical and NO damage to the brain tissue-related;④And reduce TNF-a and IL-1β content in brain tissue, reducing immune inflammatory response to neuron injury-related;⑤And improve hemorheology, increases oxygen to brain blood supply related.