| Objective The pathogenesis and treatment of senile dementia?AD?were studied from the perspective of brain and internal organs.The levels of Tau phosphorylation?Tau,p-tau Ser404?),protein?GSK-3?,CDK5?and protein phosphatase?PP1,PP2A?,the mechanism of the effect of Shiwei Wendan Decoction on the regu Lation of Tau hyperphosphorylation was studied from the behavioral,pathological and molecu Lar levels.It also provides evidence for the clinical application of Shiwei Wendan Decoction in the prevention and treatment of AD.It also provides scientific basis for the development of effective drug for the treatment of AD,and plays the multilevel of Chinese medicine compound,and the multitarget is more suitable for the unique advantage of AD complicated etiology and treatment.Method 70 Wistar rats were randomly divided into 7 groups: normal group,sham operation group,model group,donepezil group(0.33 mg·kg-1·d-1),Shiwei Wendan Decoction low-dose group(5.4 g·kg-1·d-1), Shiwei Wendan Decoction medium-dose group(10.4 g·kg-1·d-1),Shiwei Wendan Decoction high-dose group(20.8 g·kg-1·d-1),10 rats in each group.The hippocampus in rats were injected with A?1-42 to construct the AD rat model.Rats in each group were treated with 1 ml/100g/d for 28 days by means of intragastric administration.Morris water maze was used to observe the learning and memory ability of the experimental rats.The levels of Tau phosphorylation?Tau,SER404?,major protein kinase?GSK-3?,CDK5?and protein phosphate were detected by Western blot and q RT-PCR.Morris water maze was used to observe the learning and memory ability of experimental rats andthe enzyme?PP1,PP2A?expression.Results 1.In the five-day positioning navigation experiment,the escape latency of each group of rats generally showed a downward trend.There was no significant difference between the groups in the first two days.On the third day,the escape latency of the model group rats was significantly longer than that of the normal group?P<0.01?,and there was a significant difference between the Donepezil group,Shiwei Wendan decoction low,middle and high dose groups and the model group?P< 0.01?;On the 4th day,the escape latency of the model group rats was significantly longer than that of the normal group?P<0.01?.Donepezil group,Shiwei Wendan Decoction group,Shiwei Wendan Decoction high dose group and model group Compared with the donepezil group,there was no difference in the high-dose group of Shiwei Wendan Decoction?P<0.05?.Compared with the normal group,the escape latency of the model group was significantly higher than that of the normal group on the fifth day.Prolong- ed?P<0.01?,the evasion latency of each drug group was significantly shorter than that of the model group?P<0.01?.Compared with the donepezil group,there was no difference in the highdose group of Shiwei Wendan Decoction?P>0.05?.All the resu Lts of the normal group and the sham group had no difference?P> 0.05?.2.The resu Lts of the space exploration experiment on the 6th day showed that all experimental animals cou Ld rely on the clues to find the position of the platform,and their motion trajectory was at most in the quadrant of the platform.Compared with the normal group,the percentage of swimming time in the target quadrant of the model group was significantly shorter than that of the normal group,and the spatial search ability was significantly decreased?P<0.01?.Compared with the model group,there was a significant difference between the donepezil group and the traditional Chinese medicine dose group?P<0.01?.Compared with the donepezil group,there was also a significant difference between the dose group of the traditional Chinese medicine?P<0.01?.The statistics of the percentage of crossing the original platform and the quadrant show the same trend.All the resu Lts of the normal group and the sham group had no difference?P> 0.05?.3.The resu Lts of q RT-PCR and Westen Blot showed that the hippocampus Tau and SER404 in the model group were significantly increased compared with the normal group?P<0.01?;there was no difference between the normal group and the sham group?P>0.05?.Compared with the model group,the resu Lts of Tau and p-tau Ser404) in each treatment group of traditional Chinese medicine were significantly lower,with significant differences?P<0.05,P<0.01?.Compared with the donepezil group,the middle and high dose groups of Shiwei Wendan Decoction had significant differences?P<0.01?.4.The resu Lts of protein kinase and protein phosphatase experiments showed that the resu Lts of q RT-PCR and Westen Blot showed that: compared with the normal group,the levels of GSK-3? and CDK5 in the model group increased significantly?P<0.01?,while those of PP1 and PP2 A The content was significantly reduced?P<0.01?.There was no difference between the normal group and the sham group?P>0.05?.Compared with the model group,the contents of GSK-3? and CDK5 in the middle and high doses of Shiwei Wendan Decoction significantly decreased?P<0.05,P<0.01?,and the contents of PP1 and PP2 A in the medium and high dose groups of Chinese herbs increased significantly.There was a significant difference?P<0.01?.Compared with the donepezil group,there was no significant difference in the low-dose group of Shiwei Wendan decoction?P>0.05?,and there was a significant difference in the middle-and high-dose group of Shiwei Wendan decoction?P<0.05,P<0.01?.Conclusion 1.Deficiency of qi and blood,yin and yang,and dysfunction of organs are the basic pathogenesis.Obstruction of turbidity and blindness of brain palsy are important factors for the onset of senile dementia.It is an important ru Le for the treatment of dementia.2.Whether from the positioning navigation experiments reflecting spatial learning and memory acquisition ability or the spatial search experiments reflecting the information storage ability,the treatment groups can effectively improve the experimental behavioral ability of the experimental rats,but the Chinese medicine group still cannot reach.Donepezil effect.3.Shiwei Wendan Decoction can effectively improve the level of impairment of learning and memory in model rats.The mechanism may be to catalyze the dephosphorylation of tau protein,thereby inhibiting the hyperphosphorylation of tau protein,so as to improve learning and memory. |
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