Research Of Consolidating Root And Nourishing Brain Prescription Regulating RAGE/ NF-?B Signaling Pathway In Hippocampus Of The Forgetful Model In Aged Rats

ObjectTo compare the effect of consolidating root and nourishing brain treatment with treatment of nourishing spleen and nourishing brain,treatment of nourishing kidney and nourishing brain on learning and memory function of the forgetful model in aged rats and AGEs/RAGE signal pathway in their hippocampus.Evaluating comprehensively the therapeutic effects of the three kinds of treatment methods which were mentioned above.Method110 SPF healthy male SD rats were at libitum fed one week,then detecting their learning and memory function by platform.The ability of learning and memory similarities were randomLy divided into normal group with 15 and model proup with 85.Continuous intraperitoneal injection of D-glactose and NaNO2 for forty days was used to manufacture elderly forgetful rat model.In the meanwhile,normal group rats were injected with physiological saline.The 75 successful model of the rats were randomLy divided to consolidating root nourishing brain group,nourishing spleen to strengthen brain group,nourishing kidney to strengthen brain group,Western Medicine group and blank model group.Treat them respectively with prescription on consolidating root andnourishing brain,Guipiwan,Liuwei Dihuang Wan and Huperzine A once a day and a total of 20 days;Filling normal group and model group with Physiological saline.after treatment,Their learning and memory function is compared with Platform method and Morris water maze test respectively.Taking the hippopocamus from all groups,the expression of AGEs was detected by immunohistochemistry.RAGE and NF-?B p65 proteins were detected by Western blot.The contents of IL-1? and TNF-? were detected by ELISA.Result1 About the establishment of the forgetful model in aged rats.Compared to normal group,the model group rats Presented state of aging,ie;Their skin-hair were withered and,lips were dark and dry,Paws were rough,Activities were slower,appetite and psychic hygiene were poorer.In the experiment of platform,the model group rats' escape latent period were prolonged obviously?P<0.05?,while their number of errors in five minutes were more.In the Hidden Platform test of Morris water maze,the time that model group rats used to find Hidden Platform was longer?P<0.05?.And their total swimming distance was further?P<0.05?.In Probe Trains test of the Morris water maze,the times that model group rats swam through platform location?area C?was cut dowm?P<0.05?.And it took more time for them arriving target quadrant the first time?P<0.05?,while their Residence time in area C is shorter?P<0.05?.2 Influence of the consolidating root and nourishing brain method on the learning and memory function of the forgetful model in aged rats.After the treatment,compared to normal group,the model group rats' escape latent period were prolonged obviously?P<0.05?,while their number of errors in five minutes were more.In the HiddenPlatform test of Morris water maze,the time that model group rats used to find Hidden Platform was longer?P<0.05?.And their total swimming distance was further?P<0.05?.In the Morris water maze Probe Trains test,the times that model group rats swam through platform location?area C?was cut dowm?P<0.05?.And it took more time for them arriving target quadrant the first time?P<0.05?,while their Residence time in area C is shorter?P<0.05?.The results of the fed groups compared with normal group was the same as that model group compared with normal group?P<0.05?.While the fed groups Compared to model group,the results were on the other way aroud?P<0.05?.Other fed groups Compared to consolidating root prescription group,the results was the same as that model group compared with normal group?P<0.05?.There was no statistical differences of all above indices between group of nourishing spleen to strengthen brain group,nourishing kidney to strengthen brain group,western medicine group?P>0.05?.3 Effects of consolidating root and nourishing brain treatment on expression of AGEs?A?_1-42 in Rats' Hippocampus.Compared to normal group,the expression of AGEs?A?_1-42 were increased obviously in other groups except consolidating root prescription group?P<0.05?;As to consolidating root prescription group,the expression of AGEs was significantly enhanced,while A?_1-42 showed no statistical difference.Compared to model group,the expression ofAGES?A?_1-42 were decreased in the fed groups?P<0.05?;Compared to consolidating root prescription group,the expression of AGEs and A?_1-42 were enhanced in other fed groups?P<0.05?;There was no statistical significance between group of nourishing spleen to strengthenbrain group,nourishing kidney to strengthen brain group,western medicine group?P>0.05?.4 Effects of consolidating root and nourishing brain treat-ment on expression of RAGE?NF-?Bp65 in Rats' Hippocampus.Compared to normal group,the expression of RAGE?NF-?Bp65 were enhanced significantly in model group?P<0.05?;Compared to model group,the expression of RAGE?NF-?Bp65 were decreased in the fed groups?P<0.05?;Compared to consolidating root prescription group,the expression of RAGE?NF-?Bp65 were enhanced in other fed groups?P<0.05?;There was no statistical significance between group of nourishing spleen to strengthen brain group,nourishing kidney to strengthen brain group and western medicine group?P>0.05?.5 Effects of consolidating root and nourishing brain treatment on contents of IL-1??TNF-? in Rats' Hippocampus.Compared to normal group,the contents of IL-1??TNF-?were enhanced significantly in model group?P<0.05?;Compared to model group,the expression of IL-1??TNF-? were decreased in the fed groups?P<0.05?;Compared to consolidating root prescription group,the expression of IL-1??TNF-? were enhanced in other fed groups?P<0.05?;There was no statistical significance between group of nourishing spleen to strengthen brain group,nourishing kidney to strengthen brain group and western medicine group?P>0.05?.Conclusion1 After the modeling,the model group rats not only had obvious aging performance,its learning and memory ability also dropped dramatically.And it shows that the forgetful model in aged rats have been manufactured successfully.2 All of the above therapeutic methods,to a certain degree,can improve memory function of forgetful aged rats,but the effect of consolidating root and nourishing brain treatment is the best.3 Senile forgetfulness may be related with the following molecular mechanisms.Over expression of AGEs or A?_1-42 activates RAGE/NF-?Bp65 signaling pathway.The activation of RAGE/ NF-?Bp65signaling pathway can mediate the expression of a large number of inflammatory cytokines that leads to hippocampus associated inflammatory reaction.consolidating root and nourishing brain treatment,to a certain degree,can block the signal transduction of RAGE/ NF-?B signaling pathway,cut down the expression of inflammatory cytokines in hippocampus,protect the hippocampal tissue and then improve learning and memory function in elderly forgetful animal.