The Effects Of Modified Bu-Wang Powder On Cognitive Function And Its Microvascular Regeneration Mechanism In Vascular Dementia Model Rats

Objective:Vascular dementia(VaD)refers to a clinical syndrome of different degrees of dementia caused by various cerebrovascular diseases,characterized by the decline in cognitive function.In recent years,the morbidity of VaD has been increasing with the high occurrence of cerebrovascular disease.Therefore,the research on the pathogenesis and treatments of VaD are urgent.The purpose of this research mainly includes:1.To observe the effect of Modified Bu-Wang Powder(MBWP)on the cognitive function of VaD rats;2.To investigate the possible mechanism of MBWP on microvascular regeneration in VaD model rats.Methods:1.Seventy-one adult male SD rats were randomly divided into the sham operation group(Sham control,n=15)and the model group(n=56);2.VaD model rats were established by ligating the bilateral carotid arteries of SD rat(2-VO mothod),and the VaD model rats were randomly divided into the VaD model group(VaD model,n=12),the low-dose MBWP group(Low MBWP,n=12),the medium-dose MBWP group(Medium MBWP,n=11)and the high-dose MBWP group(High MBWP,n=11).The MBWP was administered orally to the the rats in each treatment group for 28 days,10 days after 2-VO operation;3.The cognitive function was evaluated by the Morris water maze and Y maze to observe the effect of MBWP on the cognitive function of VaD model rats;4.The microvessel density(MVD)in hippocampus region between each group was compared by immuno-histochemical staining;5.Using Western blotting,we analyzed the expression of HIF-1αand VEGF in the hippocampus of VaD rats.Results:1.Behavioral test:Morris water maze:(1)Oriented cruise test:The average escape latency of the VaD model group was lengthened than that of the sham-operation group from the day 2.From day 3 to day 5,the escape latency of the MBWP intervention groups was significantly shortened.And the High MBWP rats had the shortest escape latency.(2)Space exploration test:The activity time of the VaD model group in the quadrant(the IV quadrant)where the original platform was located in was significantly shorter than that of the sham-operation group(29.55±0.40%vs.59.34±0.14%,P<0.001).There was no difference of the activity time in the low-dose group and the model group(39.51±0.22%vs.29.55±0.40%,P>0.05),while the IV quadrant activity time of the medium and high-dose groups was all significantly higher than that of the model group,and the difference was statistically significant(49.71±0.24%vs.29.55±0.40%,P<0.001;55.48±0.39%vs.29.55±0.40%,P<0.001).The high-dose group had longer activity time in the IV quadrant than the middle-dose group(55.48±0.39%vs.49.71±0.24%,P<0.001).The average time and speed reaching the visual platform showed no difference among each group(P>0.05).Y-maze:The spontaneous alternation rate in the VaD model was lower than that in the sham-operation group(55.00±6.81%vs.81.5±6.72%,P<0.001).The spontaneous alternation rate of the Medium and High MBWP groups were all better than that of the VaD model group(67.75±6.50%vs.55.00±6.81%,P<0.05;76.83±5.71%vs.55.00±6.81%,P<0.001).And the spontaneous alternation rate of the High MBWP was increased than that of the Low MBWP group significantly(76.83±5.71%vs.57.14±10.78%,P<0.01).Besides,while the High MBWP group and the sham-operation group showed on difference(76.83±5.71%vs.81.50±6.72%,P>0.05).In addition,the total number of times that the animal spent in each arm showed on difference amoug each group.2.Immunohistochemical staining:When comparing with the sham-operated group,we found that the MVD in the hippocampus in VaD model group was significantly increased(25.55±2.91num./mm~2 vs.11.45±1.37num./mm~2,P<0.001).Then we compared the MVD between VaD model group and the intervention groups,and we found that the MVD showed on difference between Low MBWP group and VaD model group(27.69±1.37num./mm~2 vs.25.55±2.91num./mm~2,P>0.05),while the MVD in the Medium and High MBWP groups were increased than the VaD model rats(42.54±2.57num./mm~2 vs.25.55±2.91num./mm~2,60.45±1.54num./mm~2 vs.25.55±2.91num./mm~2,P<0.001).Compared with the Medium MBWP group,the MVD in the High MBWP group were increased(60.45±1.54num./mm~2 vs.42.54±2.57num./mm~2,P<0.001).3.Western Blot:In this part,we conjectured that the expression of HIF-1αand VEGFA in the hippocampus of the VaD model group increased than that of in the sham-operated rats,and the expression of HIF-1αand VEGFA of the MBWP intervention groups was both higher than that in the sham-operation group(P<0.05).Besides,compared with the VaD model group,the expression of HIF-1αand VEGFA in the hippocampus in the MBWP intervention groups was gradually rosed with the increase of the MBWP dose(P<0.05).Conclusion:1.The MBWP can improve the cognitive function of VaD rats with the dosage.2.The number of MVD in the hippocampus of VaD rats in the MBWP intervention groups increased with the dosage.3.The MBWP can promote angiogenesis in the hippocampus of VaD rats by up-regulating the HIF-1α/VEGF signaling pathway.