The Study Of Neuroprotective Effect And Its Mechanism Of Resveratrol On Vascular Dementia

Background:Vascular dementia is a dementia syndrome with cognitive impairment as the characteristics of the brain tissue damage caused by a series of factors of cerebral vascular cause. As the world population aging development, the number of patients with vascular dementia is increasing year by year. At present, the vascular dementia has become the main type of senile dementia in our country. The vascular dementia is not only seriously affects the patient’s own quality of life,but also caused a heavy social and economic burden on society and family. So the prevention and treatment of vascular dementia has become necessary to solve the medical and social problem. But now the pathogenesis of vascular dementia is not clear. So research in this area has become the current research hot spot. Resveratrol is a natural chemical substances which were extracted from traditional Chinese medicine Polygonum cuspidatum roots. As a natural antioxidant, resveratrol has a very broad biological effects, such as delaying tumor progression, antioxidant, protection of cardiovascula and liver, reducing blood lipid, antibacterial, antitussive,antiasthmatic.Especially the cardiovascular and neural protective effect of resveratrol has become the hotspot of research.Now the vascular and neural protective effect of rsveratro, has become a new hotspot in Department of neurology. But now the research on resveratrol is more concentratedive in neurodegenerative disease and acute cerebral vascular disease. Now there are a few of research on the effect of resveratrol on the vasuclar dementia. Resveratrol is a natural antioxidant, the anti oxidative stress effect is approved by many scholar. But now we don’t know if the resveratrol also play a protective role in anti apoptosis and cholinergic system. So in this study, we proposed to research the vascular and neural protective effect of resveratrol on the vasuclar dementia. The study consists of the following four parts of contents:Part one Protective effect of resveratrol on a PC12 cell model of oxygen-glucose deprivationObjectiveWe esteblisehed the model of oxygen glucose deprivation injury on PC 12 cells cultrued in vitro, and researched the effect of resveratrol on cell viability, LDH, MDA and SOD. To evaluate the protective effect of resveratrol on vascular dementia.MethodsBy establishing oxygen glueosedePrivation (OGD) model of PC12 cells after pretreatment with diferent concentration of resveratrol in vitro (10μmol/L,20 μmol/L, 40 μmol/L,60 μmol/L), we observed the changes of viability of the eells. At the same time, the biochemidal method was used to determine LDH activity, the activity of SOD (superoxide dismutase), the contents of MDA (malondialdehyde).ResultsCompared with the control group, the PC 12 cell activity of model group decreased significantly (P<0.05). The 10μmol/L,20μmol/L resveratrol group could significantly increase PC 12 cell activity (P<0.05), the two groups have great differences (P<0.05).. But there was no difference between the group of 40μmol/L and the model group (P>0.05). While compared with model group, the cell viability of 60μmol/L group decreased (P<0.05). Compared with the control group, the release amount of LDH increased significantly in model group (P<0.05). The 10μmol/L,20μmol/L resveratrol group could significantly decrease the release amount of LDH (P<0.05), the two groups have great differences (P<0.05). But there was no difference between the group of 40μmol/L and the group of model (P>0.05). While compared with model group, the release amount of LDH of 60μmol/L group increased (P<0.05). Compared with the control group, the activity of SOD decreased significantly in model group (P<0.05). The 10μmol/L,20μmol/L resveratrol group could significantly increase the activity of SOD (P<0.05), the two groups have great differences (P<0.05). But there was no difference between the group of 40μmol/L and the model group (P>0.05).While compared with model group, the activity of SOD of 60μmol/L group decreased (P<0.05). Compared with the control group, the content of MDA increased significantly inmodelgroup (P<0.05). The 10μmol/L,20μmol/L resveratrol group could significantly decrease the content of MDA (P<0.05), the two groups have great differences (P<0.05). But there was no difference between the group of 40μmol/L and the model group (P>0.05). While compared with model group, the content of MDA of 60μmol/L group increased (P<0.05).Conclusion10μmol/L,20μmol/L resveratrol pretreatment can improve the cell vitality of PC12 cell with model of oxygen glucose deprivation.The 40 μmol/L resveratrol had no obvious effect on the model of the cell vitality. While the 60μmol/L resveratrol can reduce the model cell vitality. And the specific protection mechanism may be related to the reduction of LDH release, increase the activity of SOD, reduce the activity of MDA.Part two Effect of resveratrol on the model of vascular dementia ratsObjectiveTo investigate the effects of Resveratrol on memory impairment in vascular dementia (VaD) rat model.MethodsThe permanent bilateral occlusion of common carotid arteries rat model was used as VaD model, The Morris water maze was used to test the spatial learning and memory performance.ResultsThe MWM test shown that the model group rats have significantly memory impairment as compared with the control group (P<0.05), and resveratrol treatment (25mg/kg oral) can inhibit the memory impairment.ConclusionThese results confirmed the neuroprotective effects Resveratrol on VaD, and that provide novel insight into the neuroprotective effects of Resveratrol and its possible therapeutic role in VaD.Part three Effect of resveratrol on the oxidative stress and cholinergic system in VD rats modelObjectiveWe intended to investigate the effects of resveratrol on MDA, SOD, GSH and the acetylcholinesterase, choline acetyl transferase in vascular dementiarat model of rat.MethodsThe MDA levels, SOD activity and GSH levels in the cortex and hippocampus were measured respectively, at the same time the he activity of AchE、ChAT in the cortex and hippocampus were measured.ResultsIn the Cortex and Hippocampus of the model group rats the increased MDA levels were increased (P<0.05) and the SOD activity and GSH levels all decreased as compared with the control group (P<0.05). Resveratrol treatment (25mg/kg oral) can inhibitthe increased of MDA levels and the decreased of SOD activity and GSH levels in VaD rat model (P<0.05). In the Cortex and Hippocampus of the model group rats the AchE levels were increased (P<0.05), the ChAT levels were decreased (P<0.05), as compared with the control group. Atorvastatin treatment can inhibit the increased of AchE levels, the decreased of ChAT levels.ConclusionThe resveratrol can inhibit the oxidative stress and stimulate the cholinergic system in the vascular dementia rat model. were measured respectively, at the same time the he activity of AchE、ChAT in the cortex and hippocampus were measured.Part four Effects of resveratrol on apoptosis in a rat model of vascular dementiaObjectiveWe intend to observe the effects of resveratrol on apoptosis associated protein in vascular dementia rats, so as to explore the protective mechanism of resveratrol on vascular dementia.MethodsAfter the completion of behavioral testing, The expression levels of Bax, Bcl-2, cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP) in the hippocampus were measured.Results.Compared with the normal group, the expression of Bax was significantly increased and theExpression of Bcl-2 decreased significantly in model group. Compared with the model group, the expression of Bax decreased significantly and the expression of Bcl-2 increased significantly in resveratrol group (P<0.05) Compared with the normal group, the expression of Caspase-3 was significantly increased in model group (P<0.05), Compared with the model group, the expression of caspase-3 decreased significantly in resveratrol group (P<0.05). Compared with the normal group, model group, the expression of PARP was significantly increased (P<0.05). Compared with the model group, the expression of PARP decreased significantly in resveratrol group (P<0.05).ConclusionResveratrol attenuated the increases in the expression levels of Bax, cleaved caspase-3 and cleaved PARP and the reductions in the expression levels of Bcl-2 that were induced by VaD.