| Objective: Vascular dementia(VD)refers to dementia caused by a variety of cerebral vascular disease(such as cerebral hemorrhage,cerebral infarction,subcortical white matter reversible lesions)that results in brain damage.It is the world's second largest type of dementia except for Alzheimer's disease.Vascular dementia can be divided into multi infarction,key parts of infarction,subcortex and other types,in those the multi infarction dementia type is the most common.Not only damage of executive ability and memory,but also mental disorders and other symptoms appear in vascular dementia.The molecular mechanism of VD includes nerve cells apoptosis,excitatory amino acids toxicity,oxidative stress,inflammation etc.In recent years,the relationship between oxidative stress and VD has been payed more and more attention by scientists.Heme oxygenase-1(HO-1)also have been known as heat shock protein,belonging to the microsomal enzyme,which is regulated by Nrf2-ARE pathway.HO-1 is closely related to oxidative stress injury.A variety of stress(such as ischemia and hypoxia,inflammation,toxins,etc.)can induce and increase the expression level of HO-1 to protect cells.The protective effects of HO-1 are closely related to metabolites.HO-1 can degradate heme into biliverdin,Co,Fe2+ and other products,and the products have anti oxidative stress effects.Recent researches have demonstrated that HO-1 plays a very important role in anti oxidative stress.Lycopene is a kind of carotenoids,which widely exists in tomato,watermelon,carrots and grapefruit etc.Lycopene is a kind of natural pigment,which is remarkable in free radical scavenging and antioxidant.As lycopene can not be synthesized in human body,it must be taken in from outside to be added.Lycopene has a vascular protective effect,as well reducing atherosclerosis,anti aging etc.It has been confirmed that lycopene has effect on Parkinson,cancer,heart disease and other diseases,but the protective effect of lycopene on vascular dementia has not yet been confirmed.We will explore the protective effect of lycopene on vascular dementia by observing the influence of lycopene on cognitive function and HO-1 expression in hippocampus tissue in VD rats,and this may provide a new way for the therapy of VD.Methods: Healthy male Sprague-Dawley(SD)rats were randomly divided into model group,control group,and lycopene group,there were 10 rats in each group.Vascular dementia model was established with the method of permanent ligation of bilateral common carotid artery.The rats in lycopene group were intragastrically given lycopene 10mg/kg/d,while the rats in model group and control group were given the same volume sodium carboxymethyl cellulose.6 weeks after,Morris water maze experiment was used to evaluate memory and learning ability of each rat.Meanwhile,the expression levels of HO-1 in the hippocampus were examined by immunohistochemical staining method and western blot method.Results:1 Influence of lycopene on ethology of VD rats1.1 The results of escape latency periodWater maze positioning and navigation experiments show that escape latency of rats were all shortened since the second day.It showed that rats of each group had a certain learning and memory ability,but the learning and memory ability were different.Results indicated that there were differences among the groups in the ability of memory and learning(P<0.05).Compared with the sham operation group,the escape latency of rats in model group was significantly prolonged in the four days(P<0.05),compared with the model group,the escape latency of rats in lycopene group were significantly shortened(P<0.05).1.2 The results of crossing platform frequencyCrossing platform frequency which represents spatial memory ability of rats was detected on fifth day,the more the crossing platform frequency was,the better the memory ability was.Compared with the control group,crossing platform frequency of rats in model group decreased significantly(P<0.05).Compared with model group,crossing platform frequency of rats in lycopene group increased significantly(P<0.05),there were no difference between control group and lycopene group(P>0.05).2 Influence of lycopene on protein expression of HO-1 in hippocampus of vascular dementia rats2.1 The results of western blotThe protein expression level of HO-1 in the hippocampus of rats: The protein expression level of HO-1 in the hippocampus of rats in model group significantly increased compared with control group(P<0.05).Compared with the model group,HO-1 protein expression levels of rats in lycopene group were significantly increased(P<0.05).Among the three groups,comparison of protein HO-1 expression levels was significantly different(F=12.36,P<0.05).2.2 The results of immunohistochemical stainingThe number of HO-1 cells in hippocampal CA1 region of rats:compared with control group,the number of HO-1 cells in hippocampal CA1 region of rats increased significantly(P<0.05).Compared with the Lycopene group,number of HO-1 cells in model group decreased significantly(P<0.05).Among the three groups,comparison of number of HO1 cells was obviously different(F=19.78,P<0.05).Conclusion:1 Lycopene can significantly decrease the escape latency and increase crossing platform frequency of vascular dementia rats,indicating that lycopene can improve the learning and memory ability of vascular dementia rats.2 Lycopene can increase the expression level of HO-1 in the hippocampal CA1 region of VD rats,suggesting that lycopene may play a protective role in protecting neurons against oxidative stress injury. |
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