| Alzheimer disease (AD) is a common degencrative disease of aged people ,which is also a cause of dementia.The clinical feature of AD is delitescence onset, hypophrenia in progress, as well as personality change.There are senile plaques (SP), neurofibrillary tangles (NFTs) and lots of neurons depletion existing in patient brain. Until now so many treating method, such as cholinesterase inhibitor, NMDA receptor antagonist and anti-inflammatory agents cannot stop advancement of AD. In the end the patients often die from some complications,such as pulmonary infections, bedsore, deep venous thrombosis and so on, which makes the AD victim and his family deep in sorrow. The emergency of neurotrophic factors (NTFs) brings new hope for AD. However, because of its large molecular weight it cannot go through BBB, doctors have to administer by cerebral ventricle, which confines its using in clinics. Recently people find some neuroprotective peptides, which have very small molecular weight, can pass through BBB easily. If administered subcutaneouly or by intravenous injection they can go into brain. The important one of them can be called NAP, which has eight amino-acid residue on the activity-dependent neuroprotective protein. Large studies have proved that NAP can protect neurons from dying through very small degree"fmol"in the cell cultures and in the brains of animal model.In Amrica the first clinical experiments manifest that nasal administering NAP is safe. But NAP also has many locals, such as unstability, short demiperiod, high price by artificial synthesis.To solve the promblems, our topic group has finished some work:the construction of NT4-NAP fusion gene; utilizing the skills of fusion gene and packing recombinant virus to construct the vector of recombinate lentivirus (rLent/NT4-NAP) which can express NAP continuely.proving nasal adminitering rLent/NT4-NAP can infect membrana mucosa nasi and improve the neurofuction of closed injury of brain mice. On the basic work of our group, this experiment is to show the neuroprotective function of NAP, through Morris water maze, morphology and biochemical indicator, meanwhile try to approch the mechanism of action.In this expriment we make some rats as the AD animal model whose left hippocamp being injeced aggregated Aβand transfer growth factorβ1 (TGFβ1). The result shows that by contrast of normal group, the memory of rats in dementia group decrease obviously, degenerations and necrosis existing in a lot of neurons, the strong masculine of AchE, and high vigor of AchE. All the results above prove that this animal model can imitate the characteristic of AD in some degree. But because it has no SP depositing in the brain, it has some disadvantiges in using.In this experiment the rats in NAP group show better memory and learning in water maze, decreased necrosis in neurons, weak masculine of AchE, low vigor of AchE. These results tell us that NAP has neuroprotective function and its mechanism maybe interacting with Aβaggregating or the system of AchE.
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