| Vascular cognitive impairment(VCI) was the change of cognitive function caused by vascular factor, including various level of cognitive impairment from moderate cognitive impairment to dementia. Chronic cerebral hypoperfusion was an important pathophysiological factor of VCI. The model of chronic cerebral hypoperfusion with permanent occlusion of bilateral common carotid arteries(2VO) in rats simulated the pathogenesis of vascular cognitive impairment. The response of oxidative stress might be the key element point of damage caused by chronic cerebral hypoperfusion. Green tea was an extremely popular drink in eastern countries. The green tea polyphenols were natural plant flavonoids found in the tea plant leaves and had many biological active effect. Green tea polyphenols could prevent cancer, drop blood fat, reduce oxidative stress response and against inflammation. To explore the effect of green tea on vascular cognitive impairment, we used a rat model of chronic cerebral hypoperfusion with 2VO to determine whether green tea polyphenols could improve vascular cognitive impairment. At the same time, we detected the change of oxidative stress response, acetylcholine esterase (AchE) and histopathology. So the mechanism of green tea polyphenols had been to be elucidated.Objective:To investigate the effect of green tea polyphenlos with various dosage on cognitive impairment in rats after chronic cerebral hypoperfusion and to explore the underlying mechanism of green tea polyphenols on chronic cerebral hypoperfusion from the aspects of oxidative stress response, AchE and histopathology.Methods:Healthy male Wistar rats were used for the study. All the rats were randomly divided into 4 groups:sham-operated group,2VO+ normal saline group (2VO+Saline), 2VO+green tea polyphenols 100mg/kg/d group (2VO+GTP100),2VO+green tea polyphenols 400mg/kg/d group (2VO+GTP400).Chronic cerebral hypoperfusion was induced by permanent occlusion of bilateral common carotid arteries (2VO) of rats. After arteries were ligated, normal saline or green tea polyphenols were administered orally by gastric intubation from the fourth week. Spatial learning and memory were assessed using the Morris water maze after the drug were given for 4 weeks. Following behavioral testing, the levels of reactive oxygen species (ROS) and antioxidative capability and the content of AchE were measured biochemically. The levels of lipid peroxidation and oxidative DNA damage in the cortex and hippocampal CA1 area were assessed by immunohistochemical staining. The mRNA and protein levels of Nrf2 were examined by real-time quantitatie polymerase chain reaction (PCR) and Western blotting. The damage of histopathology were surveyed by HE staining.Results:â‘ The escape latencies in the Morris water maze of chronic cerebral hypoperfusion rats treated with green tea polyphenols were shorten. Beginning on day 3, the escape latencies of rats treated by 400mg/kg/d green tea polyphenols were shorter than the saline-treated hypoperfusion rats. The escape latencies on day 5 were shorten in rats treated by 100mg/kg/d green tea polyphenols, which had statistical significance. The rats treated by green tea polyphenols with two kinds of dosage spent more time staying in the platform than rats with normal saline in the probe trials.â‘¡The oxidative stress response were induced by chronic cerebral hypoperfusion. Green tea polyphenols decreased the levels of malondialdehyde(MDA) and 4-hydroxynonenal(4-HNE) in the cortex and hippocampus, up-regulated the mRNA and protein levels of Nrf2, enhanced the activity of superoxide dismutase(SOD) and the capability of inhibiting hydroxy radical and total antioxidative capability(TAC) in the cortex and hippocampus, prevented oxidative DNA damage and reduced the positive cell ratio of 8-hydroxy-2'-deoxyguanosine (8-OHdG).To be treated with 400mg/kg/d green tea polyphenols had the significant effect on oxidative stress response. Green tea polyphenols had the better effect on hippocampus after chronic cerebral hypoperfusion.â‘¢The activities of AchE either in the cortex or hippocampus had no significant difference between the rats of hypoperfusion and treatment.â‘£Geen tea polyphenols lessened the damage of histopathology in the cortex and the hippocampal CA1 area.Conclusion:Green tea polyphenols can improve the cognitive impairment after chronic cerebral hypoperfusion in rats, which may be related to prevent oxidative stress response and enhance the antioxidant mechanism. The dosage(400mg/kg/d) of green tea polyphenols had the significant effects. |
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