Effects Of Genistein On CaM-CaMKⅣ Signaling Pathway In Alzheimer’s Disease Rats

Objective:This study is to investigate the effects of genistein on the study and memory ability、changes of the morphology in hippocampus、calmodulin,calmodulin dependent protein kinase kinase,calmodulin dependent protein kinase IV,p-tau of Alzheimer disease rats and to probe the probable mechanism of genistein in the treatment of Alzheimer disease.Method:Ten-month female SD rats(n=80)rats were randomly divided into sham operation group(Sham),AD model group(Model),genistein group(GS,90mg/kg)and estrogen group(EV,0.3mg/kg).The AD animal model was established after 7 days in advance with genistein,and continued to be given for 42 days.After the end of treatment,the Morris Water Maze experiment was used to record the avoidance latency,the number of times through the original platform,and the changes of learning and memory ability in AD rats was observed;HE was used to observe the morphological changes of rat hippocampus AD staining;Western blot method was used to detect AD content in rat hippocampal Ca M、Ca MKK、p-Ca MKⅣ、tau、p-tau.The statistical analysis uses SPSS for windows 15 software.Result:1.Morris water maze test showed that: compared with the sham operation group,model group rats escape latency was prolonged and the frequency of crossing the original platform location was significantly reduced,the difference was statistically significant(P <0.01);compared with the model group,genistein group and estrogen group,escape latency was shortened,frequency of crossing the original platform the position was significantly increased(P <0.01).2.HE staining showed that:the hippocampus neural cells of rats in the model group arranged disorderly,the cell space becomes larger,and the decrease in the number of cell layers,cell death occurs as part of,cell shrinkage,nuclear pyknosis,and rupture of the whole cell,deep dyed red;the genistein group of nerve cells arranged more closely,coloring uniform;estrogen group compared with the model group increased the number of neurons,cytoplasmic hyperchromatic neurons are rare.3.Western blot test results show that: compared with the sham operation group,the content of Ca M、Ca MKK、p-Ca MKⅣ in the hippocampus of the model group was the highest,and the mean light density increased obviously(P <0.01);compared with the model group,the content of Ca M、Ca MKK、p-Ca MKⅣ in hippocampus of genistein group and estrogen group decreased significantly,and the average optical density decreased significantly(P< 0.01).Compared with the sham operation group,the average optical density ratio of p-tau/tau in model group increased significantly.Compared with model group,the content of p-tau in hippocampus of genistein group and estrogen group decreased significantly,and the ratio of p-tau/tau to mean light density decreased significantly(P< 0.01).Conclusion:1.Genistein significantly improved the learning and memory ability of AD rats.2.Genistein had protective effects on the hippocampal neurons of AD rats.3.The neuroprotective effect of genistein in AD rats was mediated by inhibiting the Ca M-Ca MK IV signaling pathway and reducing the phosphorylation of tau protein.