| Chronic cerebral ischemia is a common pathological condition. It is the lack of brain blood flow perfusion for a long time caused by a variety of reasons accompanying a variety of cerebrovascular diseases'pathological processes, such as chronic cerebral ischemia, Vascular Dementia, Alzheimer, Binswanger and arteriovenous malformation. The cardinal symptom of early chronic cerebral ischemia is cognitive impairment, finally, permanent cognitive impairment and neurological deficit will be led to. Many clinical and laboratory evidence show that chronic cerebral ischemia can lead to cognitive dysfunction. With the increasing aging population, prevention and treatment of chronic cerebral ischemia caused by age-related diseases have a major social significance. Prevention of chronic cerebral ischemia disease precedes acute cerebral ischemia disease in time. So there are attached great importance to the present chronic cerebral ischemia induced cognitive dysfunction prevention research. The pathogenesis of Chronic cerebral ischemia are currently considered as in cerebral blood flow to be less than lack of cerebral blood flow and Disturbance of energy metabolism and the output of oxygen free radical and superoxide dismutase activity decrease and so on. As a result of free radical attack on cell membrane polyunsaturated fatty acid peroxidation products of a large amount of malondialdehyde. Peroxidation toxic damage to cells and enzyme produced ischemia, cytokines, such as leukocytes and endothelial cells induced the expression of adhesion molecules. Leukocyte activation and T cells go into the brain parenchyma, which resulting inflammatory response to neuronal damage. At last result the cognitive dysfunction Fasudil is a Rho / Rock signaling pathway of selective protein kinase inhibitor, in patients with acute cerebral ischemia has been confirmed. But there is little seen in the role of chronic cerebral ischemia and its mechanism. The success of this experiment in a rat model of chronic cerebral ischemia on the basis of their cognitive function in rats and the effects of free radicals in cortical. Aims to chronic cerebral ischemia induced cognitive impairment to provide a new means of prevention and treatment, and is widely used in its clinical, prevention and treatment of chronic shortage of cerebral perfusion caused by the provision of old age-related diseases based on experimental evidence.The author of this study performed Morris water maze tests before sampling to ensure that the rats can be randomly divided into sham operation group, ischemia group and Fasudil group on the premise of that there is no obvious difference in intelligence, 6 rats each group. Method we established rat chronic cerebral ischemia models is bilateral carotid communis artery occulusion with ligation. Within 48h after the operation, rats received intraperitoneal injection of 1.5ml normal saline (0.9%) at total dose of 3w. The sham operation group was blocked bilateral carotid artery without ligation. Fasudil–ischemia group received permanent bilateral carotid communis artery occulusion, as the same as chronic cerebral ischemia models, and received intraperitoneal injection of Fasudil at a dose of 7.5ml/kg every day, the total dose is 3w. The Morris water maze tests were performed to exam every group rats'learning and memory ability when the injection is at 3w, 6w and 9w, the SOD activity and CAT activity were tested by spectrophotometer, the content of MDA was tested by Thibabituric Acid TAB. The result shows that there is no obvious difference in escape latency and swim distance in sham operation group (p>0.05). When ischemia reached 3w in saline–Ischemia group, the escape latency and swim distance extended, when ischemia reached 6w and 9w, the change is obvious, which is obvious comparing that of sham operation group. When Fasudil intervene reached 3w, Fasudil–ischemia group rats'escape latency and swim distance shortened obviously than that of saline–Ischemia group (p<0.05), after intervene reached 6w and 9w, there is obvious difference between Fasudil–ischemia group and saline–Ischemia group. In sham operation group, there is no obvious difference in the activity of SOD and CAT, and the content of MDA when the intervene is at 3w, 6w and 9w (p>0.05). Ischemia led to the decrease of activity of SOD and CAT, the increase of the content of MDA in saline–Ischemia group, the difference is obvious comparing with the sham operation group. Fasudil–ischemia group rats'activity of SOD and CAT increase obviously, the content of MDA in saline–Ischemia group, the difference is obvious comparing with the sham operation group. Fasudil–ischemia group rats'activity of SOD and CAT increase obviously, the content of MDA decrease, difference is obvious (p<0.05).Schemic cerebral damage is a complex pathological process. It is generally thought that cerebral sharp metabolism, too much amount consumed of oxygen and energy is very sensitive to ischemia and absence of oxygen. A short time ischemia may lead to the functional obstacle of brain wave and nerve. The emergence of free radical theory opens out oxygen free radical's important role in some diseases'pathogenesis from molecular level. More and more research have shown that free radical takes part in damaging nerve cell in cerebral ischemia, while the most representative ones in the process of metabolism of free radical are SOD, CAT and MDA, whose activity and content reflects indirectly the change of the level of metabolism of free radical in the body.This study is based on 2VO models, learning and memory ability of rats with chronic cerebral ischemia is tested at different time. The result has shown that bilateralcarotid communis artery occlusion with ligation will decrease every indices in the Morris water maze examination which reflects rats'spatial memory ability, as time went on, rats'learning and memory ability will decrease further, which shows that at the state of chronic low perfusion, the influence of the states of ischemia and absence of oxygen on learning and memory function is gradual. After applying Fasudil intervention, comparing with Saline-Ischemia group, rats'escape latency and swim distance shortened obviously, which showed that Fasudil may improve the cognitive obstacle of rats with chronic cerebral ischemia. Then, the level change of chronic cerebral ischemia rats'epidermis free radical was observed in this examination. The result shows that the activity of rats'cortex's SOD and CAT decreased obviously, the content of MDA increased after 2VO. The activity of SOD increased at the different time, the content of MDA decreased in Fasudil-Ischemia group, the difference is more obvious than Saline-Ischemia group (p<0.05). The result of this study hints that free radical's level change is more obvious at the early stage of ischemia, and Fasudil may ameliorate chronic cerebral low perfusion caused by 2VO, the oxidative damage then decreased the damage of nerve cell, which will improve rats'learning and memory ability. The above results show that after chronic cerebral ischemia rats receiving Fasudil protection, the production of oxygen free radical in the rats'brain tissue will be decreased or the elimination will be increased, the level of active oxygen will be decreased, so the aging and death of nerve cells are decreased and stared, which show that Fasudil possesses protecting function for chronic cerebral ischemia rats.In conclusion, by medicament intervening to the rats with chronic cerebral ischemia and comparing different groups, the rats'escape latency and swim distance, and the level of free radical were tested and the conclusion is chronic cerebral ischemia will lead to the rat's cognitive obstacle, and which can be ameliorated by using Fasudil. The activity of SOD and CAT in rats with chronic cerebral ischemia declined and the content of MDA increased. Fasudil will increase the activities of SOD and CAT, and decrease the content of MDA Fasudil can improve the level of cognitive function obstacle caused by chronic cerebral ischemia through influencing the level of free radical.
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