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Study On The Mechanism Of Dementia And The Effect Of Bushen Jianpi Gaoxin Recipe On PI3K/Akt Pathway In Alzheimer's Disease Rats Based On Drug Guideline In "Compendium Of Materia Medica"

Posted on:2019-02-23Degree:MasterType:Thesis
Country:ChinaCandidate:F R YangFull Text:PDF
GTID:2334330545983206Subject:Basic Theory of TCM
Abstract/Summary:PDF Full Text Request
Objective:From the "Compendium of Materia Medica" to explore the mechanism of aging by lightening the age of drug and its point of view,and based on the perspective of the spleen and kidney failure,the scientific group prescription and the AD model rat were taken as the research object.Observing the spleen and kidney Yannian Yizhi decoction to AD model rats effects of learning and memory level,antioxidant indexes(SOD,NOS)and Ngb on PI3K/Akt pathways were explored to explore the intervention and mechanism of Spleen-kidney Yannian Yizhi on AD model,which provided experimental basis for prevention and treatment of AD by traditional Chinese medicine.And tap the academic value of "Compendium of Materia Medica".Methods:1.Literature research: Using key words such as“light weight”,“Yannian”,“forgetfulness”,“education”,“guidance”,and so on,combing “Compendium of Materia Medica” with more than 110 flavors of prolonged aging medicine,according to its main Efficacy and drug regression analysis of human aging mechanisms and lighten-ing of life,replenishing spleen and kidney drugs to delay aging.Taking dementia as the typical manifestation of aging as an example,the etiology,pathogenesis,and treatment of dementia were explored to explain the theory basis of Bushen Jianpi Yizhi in preventing and treating dementia.2.Experimental study: 70 3-month-old Wistar rats were selected and all were male.A rat hippocampus was injected with A?1-42 to establish a rat model of Alzheimer's disease.Fifty Wistar rats were selected and randomly divided into five groups: model group,donepe-zil group,spleen-kidney Yannian Yizhi decoction low dose group,and spleen kidney.Yannian Yizhi Medium-dose group,spleen and kidney Yannian Yifang high-dose group,10 in each group.Twenty Wistar rats in the same batch were randomly divided into normal group and sham operation group with 10 in each group.Rats in each group were intragastrically administered at 1 ml/100 g·d for 28 days.Morris water maze test was used to observe the ability of learning and memory in rats.The content of SOD and NOS in hippocampus were determined by chemical colorimetric assay.Immunohistochemical staining,Western blot were used to detect Ngb and PI3 K in hippo-campus of rats PI3 K,Akt and other proteins in the Akt pathway.Results:1.During the 5 day positioning test,the trend of escape latency in each group decreased,and there was no significant difference between the groups in the first 2 days.On the third day,the escape latency of the model group was significantly longer than that in the normal group(P<0.05).The high dose group and the donepezil group were significantly different from the model group(P<0.05).On the fourth day,the escape latency of the model group was signifi-cantly longer than that in the normal group(P<0.01),and the donepezil group and the spleen and kidney were extended.The evasion latency of the high dose group was significantly shorter than the model group(P<0.05).On the fifth day,the escape latency of the rats in the model group was significantly longer than that in the normal group(P<0.01),and the escape latency was significantly shortened(P<0.01)compared with the model group(P<0.01).There was no difference between the sham operation group and the normal group.2.In the space exploration experiment of 6D,it is found that except for the model group,the rest of the other groups can rely on clues to find the platform position,and the motion trajectory is most located in the platform quadrant.The model group rats swim around the pool wall,and the trajectory of the model group is less near the platform,and the trajectory of the model is randomly distributed in the quadrants.Compared with the other groups,the number of crossing the original platform significantly decreased in the model group(P<0.01).Compared with model group,donepezil group,spleen kidney and yenenyizhi prescription group increased significantly compared with model group(P<0.01).There was no difference in the ratio between the spleen and kidney,yenenyizhi Fang and middle dose group and donepezil group(P>0.05).3.The results of aging related indicators in each group showed that compared with the normal group,the NOS content in the model group increased significantly,while the SOD content decreased significantly(P<0.01).There was no difference between the normal group and the sham operation group(P>0.05).Compared with the model group,the NOS content in each treatment group decreased signifi-cantly,and the SOD content increased significantly(P<0.01).Compared with donepezil group,the contents of SOD and NOS were different in each dose group of spleen kidney Yan Nian Zhi Fang(P<0.05,P<0.01).4.The number of positive cells detected by immunohistochemi-stry showed that the number of Ngb,PI3 K and Akt in model group was significantly lower than that in normal group(P<0.01).There was no difference between the sham operation group and the normal group(P>0.05).Compared with the model group,the contents of Ngb,PI3 K and Akt in each treatment group increased significantly,with significant difference(P<0.01).Compared with donepezil group,the contents of Ngb,PI3 K and Akt in the middle and high dose group of spleen kidney Yan Nian Zhi Fang were significantly different(P<0.05,P<0.01).The average optical density results showed a basically consistent trend.5.Western Blot test results showed that compared with the nor-mal group,the number of Ngb,PI3 K and Akt in model group decreased significantly(P<0.01).There was no difference between the sham operation group and the normal group(P>0.05).Compared with the model group,the content of Ngb,PI3 K and Akt in the middle and high dose groups of the spleen and kidney yeniyiji group increased significantly(P<0.05,P<0.01),and there were some differences between the low dose group and the donepezil group(P<0.05.Compared with donepezil group,the contents of Ngb,PI3 K and Akt in each dose group of spleen kidney yenenyizhi group were different(P<0.05,P<0.01).Conclusions:1.Based on the "Compendium of Materia Medica" and the analysis of the efficacy of natural medicine,it is known that spleen and kidney deficiency is the basic pathogenesis of human aging and forgetfulness,and phlegm block is an important factor.Kidney,spleen,and phlegm can help one's body,body,and body,and it will not be old.2.Selection of "Pharmacopoeia" in the reasonable scientific group of drugs with Yannian puzzle efficacy Fangpi Yannianzhi can effectively improve the learning and memory level of rats with dementia(core symptoms of aging).3.Spleen-kidney Yannen Yizhi can effectively reduce the con-tent of NOS in the brain of rats with dementia,increase the content of SOD,increase the antioxidant capacity of brain tissue,and improve the senescence indication of AD rats.The mechanism of improvement of dementia by Spleen and kidney Yannian Recipe may be through improving PI3 K and Akt protein levels,regulating Ngb through PI3K/Akt pathway,thus reducing or repairing neuronal damage of model animal brain tissue,and improving its learning and memory impairment.
Keywords/Search Tags:Alzheimer disease, Deficiency of spleen and kidney, Compendium of Materia Medica, Kidney-tonifying and spleeninvigorating puzzle, PI3K/Akt pathway
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