| Purpose:To explore the neuroprotective effect of ginsenoside Re and breviscapine composition on vascular dementia rats based on mitogen-activated protein kinase(MAPK)signal pathway,in order to provide experimental and theoretical basis for the prevention and treatment of vascular dementia(VD)by this composition,and provide new resources and new research ideas for the treatment of VD by traditional Chinese medicine.Methods:64 stochastic rats were divided into Sham-operated group,model group,Sanqi Panax Notoginseng group(42mg/kg Sanqi Panax Notoginseng capsule 10ml/kg per day),Low-dose combination group(ginsenoside Re 2.5mg/kg breviscapine 1mg/kg per day 10ml/kg per day),Mid-dose combination group(ginsenoside Re 5mg/kg breviscapine 2mg/kg per day 10ml/kg per day),High-dose combination group(ginsenoside Re 10mg/kg breviscapine 4mg/kg per day 10ml/kg per day),Ginsenoside Re group(10mg/kg daily 10ml/kg volume),Breviscapine group(4mg/kg daily 10ml/kg volume),randomly.Each group has 8 rats.Except for the Sham-operated group,the remaining rats were establishing the VD rat model by bilateral permanent ligation of the common carotid artery.After model establishment,rats in Sham-operated group and model group were given equal volume of pure water by gavage,and the other groups were given medicine by gavage once a day for28 consecutive days.After administration to rats,learning and memory ability of rats was tested by Morris water maze,and tumor necrosis factor-α(TNF-α),interleukin(IL)-6,interleukin(IL)-βwas detected by Elisa.Western blot was used to determine the expression of Extracellular Regulated Kinase1(Erk1),c-Jun N-terminal kinase(JNK),p38 mitogen activate protein kinase(p38MAPK)proteins in the hippocampus of rats from each group.And HE staining was used to monitor the histopathological changes of the hippocampus.Results:1.Morris water maze results:(1)Morris water maze results: Rats in the model group had a longer escape latency compared to the sham-operated group(p < 0.001).In the other groups compared to the model group,no significant change in escape latency was observed in the rats of the Sanqi Panax Notoginseng group on day 1 of the localization navigation test.From day 2 onwards,the evasion latency of the rats in the Sanqi Panax Notoginseng group was considerably reduced(p < 0.01).There was a tendency to reduce the escape delay in the low-dose group of the combination,but it was not statistically significant.In the Mid-dose combination group and Breviscapine group the escape latency of the rats was shorter(p < 0.05).The escape latency of rats in the ginsenoside Re group was considerably reduced on days 1,2and 5 of training(p < 0.05),but on days 3 and 4 there were no significant differences in escape latency between the two groups;The escape latency of rats in the high dose group of the combination was considerably reduced.(p < 0.001).(2)Results of the spatial exploration test: compared with the sham-operated group,the number of times rats crossed the platform within 60 s on the 6th day of training was considerably reduced in the model group(p < 0.01).In the other groups,compared to the model group,the number of times the rats crossed the platform within 60 seconds on day 6 of training increased considerably in the Sanqi Panax Notoginseng group and high-dose combination group(p < 0.05).No significant changes were seen in the number of times rats crossed the platform within 60 seconds on the 6th day of training in the combination low and medium dose groups,ginsenoside Re group,and lanosterol group.2.Pathological results: The morphology of hippocampal nerve cells in the model group compared to the Sham group considerably,the number of brain pyramidal cells decreased.The content of cell cytoplasm decreased,and the nuclear chromatin was unclear.Most of the pyramidal cells have pyknosis,the pyknotic cells shrink as a whole,the cell body becomes darker,and the cytoplasm and nucleus are indistinguishable.Compared with the model group,the administration group can alleviate the degree of damage of brain pyramidal neurons in different degrees,and the high-dose group of the composition has more obvious protective effect on brain pyramidal cells.Under the microscope,it can be seen that the number and cytoplasm of pyramidal cells are clear and rich,and the cell nucleus is clear;Pyknosis of cells is rare in some tissues.3.ELISA results: compared with the sham-operated group,the levels of cytokines IL-1β,IL-6 and TNF-α were considerably higher in the model group(p<0.05).In the remaining groups,IL-1β content was considerably decreased in the low-dose group compared with the model group(p<0.05).IL-1β and TNF-α levels were reduced in the mid-dose group of the combination(p<0.05).IL-1β,IL-6,and TNF-α contents were considerably decreased in the Sanqi Panax Notoginseng group and the high-dose group of the combination(p<0.05).There was a tendency to decrease the content of each cytokine in the lupulin group and the ginsenoside Re group but the difference was not statistically significant.4.Western blot results:(1)Comparison of Erk1 protein content: Compared to the sham-operated group,the Erk1 protein expression level was considerably higher and statistically significant in the model group(p<0.05).In all remaining groups,Erk1 protein expression was considerably lower in the Sanqi Panax Notoginseng group and Mid-dose combination group and High-dose combination group compared with the model group(p<0.001,p<0.05,p<0.01).The difference in Erk1 protein expression in the low-dose combination group was not statistically meaningful.(2)Comparison of JNK protein levels: JNK protein expression levels were considerably higher in the model group than in the sham-operated group,which was statistically significant(p<0.05).In the remaining groups,JNK protein expression was considerably lower in the Sanqi Panax Notoginseng group and the high-dose combination group compared with the model group(p<0.05).JNK protein expression was reduced in the combination low and medium dose groups,which was not statistically significant.(3)Comparison of p38 MAPK protein levels: p38 MAPK protein expression levels were considerably higher in the model group than in the sham-operated group,which was statistically significance(p<0.05).Compared with the model group,the expression of p38 MAPK protein was considerably lower in the high dose of Sanqi Panax Notoginseng group and combination group(p<0.05).Lower expression of the p38 MAPK protein was in the Low-dose combination group and Mid-dose combination group,which was not statistically significant.Conclusions:The combination of ginsenoside Re and breviscapine can effectively improve the cognitive ability of VD rats based on MAPK signal pathway,reduce the apoptosis of hippocampal neurons in VD rats,down-regulate the expression of ERK1,JNK,p38 MAPK,and inhibit the inflammatory factor IL-1 β、 IL-6、TNF-αThe production of VD has neuroprotective effect on VD model rats. 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