| ObjectiveAt present,clinically effective drugs in the treatment of dementia are still rare.Danggui Shaoyao Decoction,a Chinese medicine from "Jinguiyaolue",composes by angelica,peony,Chuanxiong,Atractylodes,peony,and Alisma.Danggui Shaoyao Decoction originally used for the treatment of gynecological diseases and blood stasis.There are many studies reported that Danggui Shaoyao Decoction can effectively improve the clinical symptoms and the quality of life of dementia patients.There are many studies have proved that Danggui Shaoyao Decoction can effectively improve the clinical symptoms of dementia patients.These studies have proved Danggui Shaoyao Decoction has great research value in the treatment of VD.And the role of Danggui Shaoyao Decoction remains to be further explored.In this study,use bilateral common carotid artery ligation method to prepare the vascular dementia rat models.Use behavior test to detect the change of vascular dementia rats in learning and memory abilities,as well as the detection of vascular dementia rats related biochemical indicators in the body.These were to clarify the mechanism of Danggui Shaoyao Decoction on the neuroprotective effect in vascular dementia rats and the possible targets,to provide a new scientific basis in the treatment of vascular dementia.MethodIn this study,Morris water maze and fear conditioning tests were used to observe the effect of Danggui Shaoyao Decoction on learning and memory abilities in vascular dementia rat.Vascular dementia rats were randomly divided into the model group,the low-dose group of Danggui Shaoyao Decoction,the high-dose group of Danggui Shaoyao Decoction,and the positive group,12 mice in each group.12 sham-operated rats were selected as the sham group.All rats were housed in SPF grade room of Experimental Animal Center of Guangzhou University of Chinese Medicine.The low-dose group of Danggui Shaoyao Decoction was given 1.8g/Kg/d,and the high-dose group of Danggui Shaoyao Decoction was given 7.2g/Kg/d.The rats in the sham group and the model group were treated with equal volume of distilled water.All the rats were given intragastric administration one time per day,continuous administration for 4 weeks,then,followed by Morris water maze and the fear conditioning tests.Effect of Danggui Shaoyao Decoction on neuron survival in vascular dementia rat:Western Blot was used to detect the changes of apoptosis-related factors Bcl-2,Bax,Cleavage Caspase-3 in the brain of rats.The percentage of survival neurons in CA1 area of hippocampal in rats was measured by Nissl staining.Effects of Danggui Shaoyao Decoction on Oxidative Stress Related Index in vascular dementia rat:The changes of oxidative stress related index MDA,SOD and ROS in the brain of rats were detected by kit.Effects of Danggui Shaoyao Decoction on A ? transport related protein LRP1 and RAGE in the brain of vascular dementia rat:The mRNA and protein levels of LRP1 and RAGE in the brain of rats were detected by fluorescent quantitative PCR and Western Blot.The changes of A ? 1-42 in hippocampus of rats were detected by ELISA.Result1.Effects of Danggui Shaoyao Decoction on learning and memory abilities in vascular dementia ratThe Morris water maze test results showed that during the 5-day positioning navigation test,the escape latency of rats in each group showed a.tendency to shorten the training time.Compared with the model group,the escape latency of rats in sham group was significantly shorter(P<0.01),and the escape latency of the high-dose group of Danggui Shaoyao Decoction and the positive group were shorter than the model group(P<0.01,P<0.05).Compared with the model group,the number of crossing the location of the platform and the swimming distance in the target quadrant of rats in sham group were significantly increased in the space exploration test(P<0.01,P<0.01).The number of crossing the location platform and the swimming distance in the target quadrant of rats in the high-dose group of Danggui Shaoyao Decoction and the positive group were also higher than those in the model group(P<0.01,P<0.05;P<0.05,P<0.05).The results of the fear conditioning test showed that there was no significant difference in the freezing time between any two groups on the 3h test(P>0.05).On the 24h test,compared with the model group,the freezing time of the sham group was significantly higher(P<0.01),and the freezing time of the high-dose group of Danggui Shaoyao Decoction was also higher than the model group(P<0.05).2.Effect of Danggui Shaoyao Decoction on neuron apoptosis-related protein in the brain of vascular dementia ratThe Western Blot test results showed that compared with the model group,the ratio of Bcl-2 and Bax protein in the brain of the high-dose group of Danggui Shaoyao Decoction and the positive groups were significantly higher(P<0.01,P<0.01).And compared with the model group,the expression of Cleavage Caspase-3 in the brain of the high-dose group of Danggui Shaoyao Decoction and the positive groups were significantly higher(P<0.01,P<0.01).The Nissl staining results showed that compared with the model group,the percentage of survival neurons in CA1 area of hippocampal of the high-dose group of Danggui Shaoyao Decoction and the positive groups were significantly higher(P<0.05,P<0.05).3.Effect of Danggui Shaoyao Decoction on oxidative stress in the brain of vascular dementia ratThe kits detected results showed that compared with the model group,the level of MDA in the brain of the high-dose group of Danggui Shaoyao Decoction and the positive groups were significantly lower(P<0.01,P<0.01),the activity of SOD in the brain of the high-dose group of Danggui Shaoyao Decoction and the positive groups were significantly higher(P<0.05,P<0.05),and the activity of ROS in the brain of the high-dose group of Danggui Shaoyao Decoction and the positive groups were significantly lower(P<0.01,P<0.01).4.Effect of Danggui Shaoyao Decoction on A ? transport-related protein LRP1 and RAGE in the brain of vascular dementia ratThe Fluorescence quantitative PCR results showed that compared with the model group,the mRNA level of LRP1 in the brain of the low-dose,high-dose group of Danggui Shaoyao Decoction and the positive groups were significantly higher(P<0.05,P<0.01,P<0.05).There was no significantly changed in the mRNA level of RAGE between any two experimental groups(P>0.05).The Western Blot test results showed that compared with the model group,the protein level of LRP1 in the brain of the low-dose,high-dose group of Danggui Shaoyao Decoction and the positive groups were significantly higher(P<0.05,P<0.01,P<0.05).There was no significantly changed in the protein level of RAGE between any two experimental groups(P>0.05).The ELISA results showed that compared with the sham group,the level of A ? 1-42 in the hippocampus of model group was significantly higher(P<0.05).However,There was no significantly changed in the level of A? 1-42 between any two drug groups(P>0.05).ConclusionThe behavior test results showed that Danggui Shaoyao Decoction could improve the learning and memory abilities in vascular dementia rat.Biochemical detects and morphological results showed that Danggui Shaoyao Decoction may play a neuroprotective role by regulating the apoptosis-related proteins and the oxidative stress-related indexes in the brain of vascular dementia rat.The effect of Danggui Shaoyao Decoction on the expression of RAGE protein in the brain of VD rats was not obviously,and the content of A? in hippocampus of rats also did not change significantly,but Danggui Shaoyao Decoction may still play a role through other mechanisms associated with LRP1.The results of this study indicate that Danggui Shaoyao Decoction has the potential to bring new therapeutic strategies in the treatment of vascular dementia. |
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