The Dynamic Changes Of RAAS In The Vascular Dementia Model Rats And The Brain Protection Effect Of Its Inhibitors

Objective: To observe the renin- angiotensin-aldosterone system(RAAS) in the vascular dementia model rats and the inhibitors of the renin – angiotensin system on the protective effects of the vascular dementia model rats, to explore the developing changes of renin – angiotensin system in vascular dementia model rats, and further to reveal its action mechanism.Method: 1. Filtering normal memory male SD rats 80 with the water maze, randomly assigned into the experimental groups, each group 10: control group, model group 1d, model group 3d, model group 7d, model group 14 d, model group 21 d, model group 30 d. not ligating common carotid arteries as normal control group, the operation model groups in different time were about to ligate common carotid arteries as the time of experiment. After surgery, all rats of experiment freely to eat, drink.When to the time of experimental design,all experimental rats fasting overnight, weighing, randomly selected 5 in each group,1﹪pentobarbital sodium anesthesia(0.3 ml·100 g- 1), collecting blood of the abdominal aorta, after collecting the blood, beheading, getting cerebral cortex and hippocampus and making homogenate separately. Respectively, using the method of RIA(Radioimmunoassay, RIA) to detect the levels of Renin, Angiotensin II, Aldosterone in the homogenate of plasma, cortex and hippocampus;Another part after anesthesia, with 4 ﹪ paraformaldehyde fixed, fixed in brain after the break, paraffin embedding, slice of HE staining under light microscopy to observe the pathological changes.2. Filtering normal memory male SD rats 60 with the water maze, not ligating common carotid arteries of normal control group, the operative model groups were ligated common carotid arteries respectively in different time, after the success of the surgery, randomly assigned into the experimental group, each group 10: control group, the operation model group(30d), aliskiren group and enalapril group, candesartan group. Rats of each group freely to eat and drink, and in accordance with the 1 ml·100 g- 1 to gavage, giving corresponding drugs respectively, control group and the operation model group(30d) were given equal capacity of distilled water.Timing starts from gavage, continue to fill the gavage for 30 days, water maze experiment to observe groups in the dementia model group, the control group and the treatments of drugs group; Executed after anesthesia, randomly selected 5 in each group,taking blood from abdominal aorta, after taking blood, beheading,collecting cerebral cortex and hippocampus and making homogenate seperately, respectively, using the method of RIA(Radioimmunoassay, RIA) to detect the levels of Renin, Angiotensin II, Aldosterone in the homogenate of plasma, cortex and hippocampus;Another part after anesthesia, with 4 ﹪ paraformaldehyde fixed, taking brain after the break, the embedding slice to detect apoptosis by TUNEL method, observation of brain damage, using IPP image processing software to determine the integral optical density(IOD) of slice.Results: 1. Surgery group(30d) and control group water maze data comparison,there was significant difference(p < 0.05); the renin activity and angiotensinⅡ of cortex, hippocampus and plasma in each time group compared with control group, the level of overall showed a trend of increase, the change of the level of ALD was wavy, the renin activity, angiotensinⅡand ALD in cortex and hippocampus were no linear correlation with plasma;Brain tissue then pathology observation found that :On ischemia time the cerebral cortex and hippocampal cells distribution density was reduced, nuclei deformation showed pleomorphism, nucleus pycnosis, dissolved.2. Water maze experiment, the operative model group(30d) compared with control group,the spatial memory ability was weaker, and had significant difference(p< 0.05), the space memory ability in treatment groups increased and therewere significant differences(p < 0.05), there was no significant difference compared with control group, there was no significant difference between drug groups; Compared with normal group, model group(30d), cortex and hippocampus plasma renin activity and angiotensin Ⅱ(Ang Ⅱ) and aldosterone(ALD) levels were increased with significant difference(p < 0.05);Compared with model group(30d), aliskiren group plasma, cortex and hippocampus of renin activity and angiotensin Ⅱ(Ang Ⅱ) and aldosterone(ALD) levels were lower with significant difference(p<0.05), plasma, cortex and hippocampus of enalaprilat group angiotensin Ⅱ(Ang Ⅱ) and aldosterone(ALD) levels were lower with significant difference(p < 0.05), plasma, cortex and hippocampus candesartan group aldosterone(ALD) levels were lower with significant difference(p < 0.05);Compared with the normal group, model group(30d) of cortical and hippocampal cells distribution density lower, nuclear pyknosis, increased apoptosis positive;Compared with model group(30d), treatment groups of cortical and hippocampal cells reduced the degree of distribution density, reduced apoptosis positive staining. Compared with normal group, the IOD of model group(30 d), aliskiren group, enalapril group and candesartan group was enhancement, there were significant differences(p < 0.05);Compared with model group(30d), the IOD of aliskiren group, enalapril group and candesartan group abated with significant differences(p < 0.05).Conclusion: Different time respectively ligating common carotid arteries to build vascular dementia model of rats is successful, renin- angiotensin- aldosterone system plays an important role in the development of the occurrence of cerebral ischemia, the inhibitors of renin angiotensin aldosterone system have certain improvement effects on cerebral ischemia, can protect neurons, reduce ischemic damage in the cortex and hippocampus.