Mechanism Of Ginsenoside Rg1 In Improving Cognitive Dysfunction In AD Tree Shrews

Objective:In this experiment,D-galactose combined with Aβ25-35-induced AD dendrimer model was firstly selected to study the therapeutic mechanism of ginsenoside Rg1 derived from Panax notoginseng drugs for AD.Further enriched the experimental animal model of AD,and provided basic data for the development and application of the Sanqi drug.Method:The experiment was divided into two parts.The first part was the establishment of the AD tree model:40 male trees were randomly divided into control group(CT),D-galactose group(D),Ap group(A),D-galactose combined with Aβ25-35(D+A).Tree shrews were anesthetized with 3%pentobarbital(30 mg/kg/d,im).All tree stalks are fixed in the stereo positioner and cut to the beginning.The hippocampus(Hipp)was localized according to the stereotactic map,and 4 μl of Aβ25-35(5 mg/ml)was injected into the hippocampus of group A and group D+A once;4 μl of normal saline was injected into the hi-ppocampus of group CT and D..For group D and group D+A,D-galactose(125 mg/kg/d,sc)was injected subcutaneously every day after surgery,while the CT group and group A were injected subcutaneously with the same dose of normal saline for 8 weeks.The water maze behavioral test was performed at the 9th week.After anesthesia,the tree shrews were sacrificed,and the brain was embedded in paraffin and sectioned(5 μm)for use.IHC was used to detect the expression of Aβ1-42.The second part is the mechanism of improving the cognitive dysfunction of AD tree ginseng ginseng saponin Rgl.The 60 healthy male tree shrews were randomly divided into 6 groups:CT group,D+A group,D+A+Donepezil.(DN)group,ginsenoside Rgl low,medium and high dose groups(L,M,H).The tree shrews anesthetized by 3%pentobarbital were fixed in a stereotactic apparatus,and 4 μl of Aβ25-35(5 mg/ml)was injected into the hippocampus of D+A,DN,L,M and H groups,CT group.Inject the same amount of normal saline.D-galactose(125 mg/kg/d,sc)was administered daily to D+A group and normal saline(3ml/kg/d,ig)was administered.D-galactose was administered to DN and donepezil(3mg/Kg/d,ig),L,M,H group were injected with D-galactose and administer low,medium and high doses of ginsenoside Rgl(7.5,15,30 mg/kg/d,ig),and the CT group was injected subcutaneously.Sauce the same-amount of normal saline.After 8 weeks,the water maze test was performed,the animals were anesthetized,half-brain paraffin-embedded sections were taken,HE staining was performed,and Aβ1-42,SOD1 expression was detected by IHC.The remaining hemispheres were tested for expression of APP,BACE1,and SOD1 by WB.Results:The first part:D,A,D+A group tree mites have cognitive impairment,increase the expression of brain Aβ1-42 Compared with group D and group A,the pathological features of D+A group were more significant.We used D+A composite factor modeling method as the modeling method of Rgl treatment experiment.In the MWM experiment,compared with the CT group,the escape latency of D,A,D+A group was significantly significantly prolonged(P<0.01),while the escape latency of D+A was significantly longer than that of group D and group A(P<0.05).In the experiment of crossing the platform,the number of crossing platforms in D.A and D+A groups was significantly lower than that in CT group(P<0.05),while the number of crossing platforms in D+A group was significantly lower than that in D group and A group(P<0.05).By immun-ohistochemistry,Aβ1-42 was significantly increased in the hippocampus and cortex of the D,A,D+A groups compared with the CT group(P<0.05),while the Aβ1-42 in the D+A group was significantly higher than the D group.And group A(P<0.05).Part Ⅱ:Ginsenoside Rgl extracted from Radix Notoginseng to improve co-gnitive dysfunction of AD tree shrews1.In the MWM,compared with the D+A group,the escape latency of the L,M,H and DN groups was significantly lower(P<0.01);compared with the L group,the escape latency of the M and H groups was significant on the fo-urth day.The decrease was(P<0.05),and on the 5th-6th day,the significance was significantly decreased(P<0.01).In the platform experiment,the number of crossing platforms in the L,M,H and DN groups was significantly higher than that in the model group(P<0.05);the number of crossing platforms in the M and H groups was significantly higher than that in the low dose group(P<0.01).2.In the IHC results,M,H and DN groups could reduce the expression of Aβ1-42 in the model tree,which was significantly lower than that in the D+A group(P<0.05).Compared with the L group,M The Aβ1-42 of the H group was significantly lower(P<0.05),which was significantly better than the L group.3.In the HE staining results,the neurons in the D+A group were concentrated,and the cell damage was severe.The M,H and DN groups could alleviate cell damage.4.In the WB test results,there was no significant difference in the expres-sion of APP between CT,L,M,H and DN groups compared with D+A group(P>0.05).Compared with D+A group,the expression of BACE1 in M,H an-d DN groups was significantly lower(P<0.05).The expression of BACE1 in M and H groups was significantly lower than that in L group(P<0.05).5.In the IHC results,the expression of SOD1 in L,M,H and DN group-s was significantly higher than that in D+A group(P<0.01).The expression of SOD1 in M and H groups was significantly higher than that in L group.Incr-eased sexual(P<0.05),significantly better than the L group.The results of WB showed that the expression of SOD 1 in L,M,H and DN groups was significantly higher than that in D+A group(P<0.05).The expression of SOD1 in M and H groups was significantly higher than that in L group(P<0.05),significantly better than the L group.6.In the WB results,the L,M,H and DN groups increased the ratio of Bcl-2/Bax and inhibited the expression of cleaved-caspase3,which was significantly different from the D+A group(P<0.05);M and H groups The ratio of Bcl-2/Bax to cleaved-caspase3 was significantly different from that of L group(P<0.05),which was significantly better than L group.Conclusion:D-galactose combined with Aβ25-35 induced model tree shrews,which accords with the characteristics of AD in behavior and pathology,and the learning and memory ability of tree shrews is reduced,which can be used for model establishment.Ginsenoside Rgl,a extract of Panax notoginseng,can improve cognitive dysfunction and protect neurons in the tree shrew model.