The Relationship Of Kidney Deficiency And Phlegm Stasis With AD, And The Research For The Therapy Of Replenishing Kidney-Essence And Removing Phlegm To Benefit Wisdom Method To AD

Objective:Alzheimer’s disease(AD) is a kind of onset conceals the progressive development of the nervous system degenerative disease.It is the most common cause of dementia and the most common senile dementia. Characteristics of AD include progressive memory disorders,cognitive dysfunction,personality changes,and language barrier neuropsychological symptoms.Therefore,to strengthen the research of the etiology and pathogenesis of AD,seeking valuable drug and effective prevention measures has important realistic significance and clinical value.Based on the basic pathogenesis of this subject is to interpret the AD exploring fundamental law, using APP/PS1 double transgenic mice as AD animal model,to observe the effect and mechanism of Bushenhuatanyizhifangreplenishing kidney-essence and removing phlegm to benefit wisdom method to treat AD,in-depth study of traditional Chinese medicine in the treatment of AD to provide experimental evidence and theoretical basis. Method:1.Theoretical discussion:Sorting out literature of ancient and modern,on the AD recorded, summarized TCM understanding of AD pathogenesis,combined with modern medical research is given priority to with kidney deficiency and AD relationship,the relationship between kidney and phlegm obstruction,explain the basic pathogenesis of Alzheimer disease(AD)and therapeutic treatment.2.Experimental study:Choosing the APP/PS1 double transgenic mouse model,targeting Aβ deposition to study the mechanism between kidney-essence and removing phlegm to benefit wisdom method and AD.Morris water maze experiment, jumping platform experiment,shuttle box test are employed todetect mice behavior changes;Transmission electron microscope is used to observe the changes of hippocampal neurons and synapses in mice;Use immunohistochemistry to observe the mice hippocampus Aβ1-40, Aβ1-42 dyeing change, adopt Western Blot and immunohistochemistry assay to observe the expression of secrete enzymes and degrading enzymes released mainly by Aβ(α-secrete enzymes:ADAM-10,β- secretase:BACE1,degrading enzymes:NEP, IDE),affecting the expression of RAGE、LRP1 and hippocampal NF-κB.Use ELISA test to detect the contents of IL-1β,TNF-α.Use flow cytometry to detect the changes in the contents of groups of mice peripheral blood adhesion molecules(CD11a、CD11b、CD18、CD54、CD62L). Results:Morris water maze experiment showed that in the process of the whole navigation experiment,after giving Bushen Huatan Yizhi prescription, the APP/PS1 double-transgenic mice can find escaping platform faster, And as the training time extension,learning trend is constantly strengthened,especially in high dose group.In spatial probe test,compared with model group,with the Bushen Huatan Yizhi prescription group, the number of crossing the platform, the first quadrant time of mice increased significantly(P< 0.01, P< 0.05)and the crossing platform time decreased significantly(P< 0.01).Jumping platform experiment showed that compared with model group,the incubation period of the medicated group is reduced significantly and the number of errors of mice decreased significantly(P<0.01).Shuttle box experiment showed that, compared with model group, the number of active avoidance of mice with Bushen Huatan Yizhi prescription group increased significantly(P < 0.01, P < 0.05), and active avoidance incubation period, the passive avoidance incubation period are reduced significantly(P<0.01).The therapy of replenishing kidney-essence and removing phlegm to benefit wisdom method can improve the APP/PS1 double transgenic mice memory.By transmission electron microscope,with Bushen Huatan Yizhi prescription group can protect hippocampal neurons and synapses; Immunohistochemistry results show that compared with the blank group, the model group Aβ1-40、Aβ1-42 dyeing cell number increased obviously, dyeing is deeper, and the model group showed occasional senile pigment dyeing. Compared with model group, the drug group Aβ1-40、Aβ1-42 dyeing less number of cells(P< 0.05), dyeing shallow.Immunohistochemical and Weston- blot results show that compared with the blank group, model group, ADAM-10, the NEP,IDE expression significantly lower(P< 0.05, P< 0.01). Compared with model group, each dose group of ADAM-10, the NEP, IDE expression significantly higher(P< 0.05, P< 0.01). Compared with the blank group, model group, Weston- blot shows BACE1, RAGE, LRP- 1, the NF-κB expression significantly increased(P<0.05, P< 0.01).Compared with model group, each dose group of BACE1 there was no significant difference(P> 0.05), and RAGE,LRP1, the NF-κB expression significantly lower(PP<0.05, P<0.01).ELISA test results show that, compared with the blank group, model group mice hippocampus IL-1β and TNF-α increased significantly(P< 0.01);the rest each dosage group rats,Compared with model group, hippocampal IL-1β and TNF-α decreased significantly(P<0.01, P <0.05).Flow cytometry instrument test results show that compared with theblank group,model group mice peripheral blood adhesion molecule CD11 a,CD11b,CD18,CD54,CD62 L content were significantly lower(P<0.05, P<0.01);compared with model group,each dose group of peripheral blood adhesion molecules CD18,CD54 levels were significantly higher(P<0.05, P<0.01),while CD11 a,CD11b,CD62 L content has no obvious difference(P>0.05). Conclusion:1.The kidney deficiency is related to the pathogenesis of AD,phlegm obstruction is one of the pathogenesis of AD.The therapy of replenishing kidney-essence and removing phlegm to benefit wisdom method is an important treatment of prevention and treatment of AD.2. Bushen Huatan Yizhi prescription can improve the ability of learning and memory in the APP/PS1 double-transgenic mice,and has a certain protective effect on the hippocampus neurons and synapses.3.The mechanism of action of Bushen Huatan Yizhi prescription with AD are related to reduction of Aβ produced by APP/PS1 double-transgenic mice hippocampus, accelerating the degradation and delivery of Aβ,reducing inflammation and regulating the serum adhesion molecule.