The Mechanism Study Of Neuropretection Of RHu-EPO On Alzheimer’s Disease Rats Induced By Aβ1-42

Background and PurposeAlzheimer’s disease (AD) is common in the elderly population. The main clinical manifestations is of progressive memory loss, cognitive impairment and dementia;the pathological change is senile plaques(the SP) in the neocortex and hippocampus, inside the neuron there are neurofibrillary tangles (NFT) to be found as well as cholinergic neurons and synaptic loss. age was positively related to AD, Along with China entered the aging society, AD has become the major diseases behind cardiovascular disease, cancer and stroke, it has became another serious harmful problem to the elderly person. the pathogenesis of AD is not clear, nor have effective clinical theraputical drugs. Therefore, to find new effective control methods and drugs has became the important issue of medical research in this field.Erythropoietin (EPO) is a glycoprotein cytokine, which can stimulate the bone marrow erythropoiesis, the United States initially mainly used it for the treatment of anemia results in renal disease and cancer in clinical practice. In recent years, a large number of experimental studies confirmed that the functional EPO and its receptor are expressed in neurons, glial cells and vascular endothelial cells, so we can say it is a cytokine with multiple functions, and with a wide range of the growth-promoting and protective effects on the nervous system disease,especially in the treatment of neurodegenerative diseases.In this Study, we observed the effective role of rHu-EPO on AD rats induced by Aβ1-42and explore the possible mechanisms.Methods and Results1Effects of RHu-EPO on spatial memory and learning ability of AD rats induced by Aβ1-42and its mechanismTo explore the effects of rHu-EPO on spatial memory and learning ability of AD rats induced by Aβ1-42and its mechanism. Methods:96Wistar rats were randomly divided into4groups:saline group (hippocampus injected with saline), the AD model group(hippocampal injection of Aβ1-42)、rHu-EPO treatment group (Intraperitoneal injection rHu-EPO after the success of model making) and piracetam treatment group (Intraperitoneal injection piracetam after the success of model making). The spatial memory and learning ability of the rats was tested with Morris water maze; the level of Synapsinl expression were observed by Western blotting in each group. The results showed that:compared with the saline group, rHu-EPO treatment group and piracetam treatment group, the Morris water maze test of the AD model group was significantly prolonged(P<0.05), compared with rHu-EPO treatment group and the piracetam group and saline group showed no significant difference (P>0.05); Synapsinl:rHu-EPO treatment group was significantly higher than the AD model group (P<0.05), compared with rHu-EPO treatment group and the piracetam treatment group and saline group showed no significant difference (P>0.05). These findings suggest that rHu-EPO can significantly improve learning and memory ability in AD rats induced by Aβ1-4, which may through upregulation Synapsin1protein expression.2Effects of rHu-EPO on Apoptosis-related Proteins XIAP and Bcl-XL in Hippocampus Neurons of AD Rats Induced by Aβ1-42 To explore the effects of rHu-EPO on apoptosis-related proteins XIAP and Bcl-XL in hippocampus neurons of AD rats induced by Aβ1-42.Methods:96Wistar rats were randomly divided into into4groups:saline group, the AD model group, rHu-EPO treatment group and piracetam treatment group. the levels of apoptosis related proteins XIAP and Bcl-XL expression were observed by Western blotting and Immunohistochemistry seperately. The results showed that:compared with the saline group, the AD model group XIAP and Bcl-XL expression was slightly lower;compared with the AD model group, the XIAP and Bcl-XL expression of rHu-EPO treatment group and piracetam treatment group were markedly increased(P <0.05); However, the expression of Bcl-2between the rHu-EPO-treatment group and piracetam treatment group showed no signaficant difference(P>0.05);the results suggest that rHu-EPO can increase the expression of XIAP and Bcl-XL, to play the anti-apoptotic and protective role.3Effects of rHu-EPO on cortical neuron dendritic spines of AD Rats Induced by Aβ1-4232Wistar rats were randomly divided into saline group, the AD model group, rHu-EPO treatment group and piracetam treatment group, each group was observed the Quantitive and components changes in cortical neuron dendritic spines of the rat.The results showed that:compared with the saline group, the number of dendritic spines of AD model group were decreased, the number of rHu-EPO treatment group and piracetam treatment group significantly increased than that of AD model group; the result suggest that:rHu-EPO can reduce the destruction of the dendritic spines of rat cortical neurons to improve cognitive abilities in rats caused by Aβ1-42.ConclusionrHu-EPO could improve the learning and spatial memory ability of AD rats induced by Aβ1-42.which may be through increase Synapsinl expression; raising the expression of XIAP and Bcl-XL, inhibit neuronal apoptosis of hippocampal neurons; increase the number of dendritic spines of cortical neurons; promote nerve excitability and neurotransmission.The findings above provide experimental evidences for further understanding of the exact neuroprotective mechanism of rHu-EPO in the prevention and treatment of AD.