Sheng-Jiang-San’s Clinical Study And Experimental Research On The Treatment Of Vascular Dementia

Objective:This dissertation aims to study the curative effect and mechanism of Shengjiangsan in curing vascular dementia(VD)from clinical applications and experiments.In the clinical perspective,the effect on the VD patients are measured under the random,comparative and parallel principles;in the experimental perspective,influence on the memory ability of the VD rats and molecular mechanisms of nerve protection of the Shengjiangsan will be observed in both animal experiments and in vitro experiments,possibilities of the mechanism will be discussed as well.Methods:In clinical study,120 VD patients in our hospital were selected and divided randomly into two groups of 60,one was the Powder Group,and the other Control Group.During the 12-week treatment,both groups were given nimodipine,oxiracetam and huperzine while the Powder Group were given the Shengjiangsan.Effects were measured by comparing the scores of MMSE,common carotid RI,ID detection value,serum IL-1β,TNF-α level and ADL score difference before and after.In animal experiments,VD rats were divided randomly into Regular Group,Sham operation Group,Model Group,Positive Medicine Group(donepezil,1 mg·kg-1),and Powder Groups of low,middle,high dosages(0.67,1.33,2.66 g·kg-1),ten rats in each group.Chronic cerebral ischemia VD models were made with improved 2VO method in all the groups except the Regular Group and Sham-operation Group,medicines were given for eight weeks in a row one week after the operation.Then,the influence of Shengjiangsan on the rats’abilities of memory,place navigation and space exploration was observed and analyzed;pathomorphism in hippocampus was studied by HE staining;the levels of VEGF,Nestin,Wnt,p-LRP,p-GSK3β and β-catenin were tested by western blot and immunofluorescence staining,and the protection mechanism of Shengjiangsan in the hippocampus of the VD rats was probed preliminary.In the in vitro experiments,neural stem cells were divided into Regular Group,Model Group,Low Powder Group(0.5mg/ml),Middle Powder Group(1mg/ml)and High Powder Group(2mg/ml),then,neural stem cells were inoculated in six well plates,when the concentration was suitable all the groups except Regular Group were given medicines of different concentrations.After 24 hours,protein was extracted from cells,the protection mechanism of Shengjiangsan in the hippocampus of the VD rats was probed preliminary through Western blot,VEGF and Nestin.Results:1.In the clinical application,MMSE score,common carotid RI,ID detection value and ADL score difference in all the groups were statistically insignificant(P>0.05)before the treatment,however,after the treatment the abilities of navigation,reminiscence,language,the total score of MMSE,common carotid artery ID values and ADL value in the Powder Groups were higher over the Control Groups(P<0.05),serum IL-1β and TNF-a level in the Powder Groups were lower than the Regular Groups(P<0.05).After the treatment,the total effective rate of the Powder Group reached 93.33%(56/60),while the Control Groups remain 80%(48/60),this difference was statistically significant(P<0.05).2.In the animal experiments,the Powder Groups of different dosages prolonged the incubation period of dark avoidance task,meanwhile shortened the incubation period of place navigation and space exploration of the VD rats.The Shengjiangsan promoted the pathological damage repair in hippocampus and expressions of VEGF and Nestin,and increased the levels of Wnt,p-LRP,p-GSK3β and β-catenin,which were statistically significant(P<0.05,P<0.01).3.In the in vitro experiments,hippocampus model was built,and the Shengjiangsan promote the expressions of VEGF and Nestin in the hippocampus.Conclusion:1.Shengjiangsan has preferable clinical effect in curing VD patients combining with nimodipine,oxiracetam and huperzine,and can significantly enhance the cognitive functions and activity of daily living.2.The improvement of the VD rats’ ability of memory and space identity may have relationship with activating Wnt pathway of hippocampus.3.The improvement of the VD rats’ ability of memory and space identity may have relationship with promoting the expressions of VEGF and Nestin in hippocampus.