The Influence Of TEN On Cerbral Neuronal Cells Apoptosis And Tau Protein Hyperphosphorylation In AD Model Rats Induced By β-amyloid Protein 1-40

Alzheimer's disease (AD) is a kind of neurodegenerative disease, with pathologic features including senile plaque, neuronal degeneration or loss and neurofibrillary tangles. With the global acceleration of aging, the incidence of AD becomes increasingly pronounced, which takes more and more burden to family and society. AD becomes a more concerned research topic in researchgeriatrics and neuroscience. Therefore investigateing its pathogenesis, developing new drugs are imperative.Objective:1 To research the protection of TEN to the toxic effect and injury effect on rat cerbral neuronal cells induced by Aβ1-40.2 To research the effects of TEN on apoptosis proteins Bcl-2, Bax, Caspase-9 and Caspase-3 in rat cerbral neuronal cells induced by Aβ1-40.3 To research the effects of TEN on tau protein hyperphosphorylation in rat cerbral neuronal cells induced by Aβ1-40.Methods:1 Inject Aβ1-40 into the Rat hippoCamPaⅠto establish the model of AD, the rats were given to continual intragastric administration for 25 days. Observe the toxic effect and injury effect of Aβ1-40 on the Rat cerbral neuronal cells and the protection of TEN to it with HE and nissl staining.2 Observe the effects of TEN on apoptosis proteins Bcl-2, Bax, Caspase-9 and Caspase-3 to AD model rats cerbral neuronal cells with Immunohistochemical stain.3 Observe the effects of TEN on tau, PKA, PP-2A to AD model rats cerbral neuronal cells with Immunohistochemical stain, indirect immunofluorescence labeling method.Results:1 Establishing AD model 25 days later, compared with the sham-operated group the quantity of neuron of the model group was less, nuclear pycnosis and was little, cell body degraded, nucleole was in nubibus, cytoplasm was less. After treatment for 25 days, compared with the model group nerve cells obvious increased and eumorphism. It showed that the injury degree became better. 2 The results of ICH showed that the expression of Bcl-2 in AD model and TEN groups significantly increased compared with the sham-operated group, the expression of Bcl-2 in high and middle TEN groups were significantly higher than it in model group, which showed that maybe nerve cells depress apoptosis deduced by Aβ1-40 through up-regulation of Bcl-2 protein expression. The expressions of Bax in AD model group were higher than it in the sham-operated and TEN groups, making the ratio of Bax/Bcl-2 decreasing. On the other hand, the expression of Caspase-3 and Caspase-9 in model and TEN groups were significantly higher than it in the sham-operated group, which showed that intrinsic pathway of apoptosis has effect in the pathogenic process of AD.3 The expression of tau is significantly higher than it in model and TEN groups compared with the sham-operated group. The expression of PKA is significantly higher than it in model groups compared with the sham-operated group and TEN groups. The expression of PP-2A is significantly higher than it in the sham-operated group and TEN group compared with model group. It showed that PKA and PP-2A were indeed involved in the process of tau protein hyperphosphorylation.Conclusion:1 It will cause neurotoxicity and cell injury when Aβdeposit in the brain. It showed that TEN has inhibitory effect on the neurotoxicity caused by Aβ, has some protection to cell injury.2 Apoptosis is a critical mechanism in AD. It showed that TEN can inhibit apoptosis caused by AP1-40. Maybe it protect cerbral neuronal cells through regulating Bcl-2 family and Caspase family genes expression.3 NFT is a pathological features of AD, which caused by tau protein hyperphosphorylation. It showed that TEN may up-regulate PP-2A expression, down-regulate PKA expression, which can keep the balance of tau protein phosphorylation and dephosphorylation.