| Background:AD, which was namedas Alzheimer’s disease. It is a kind of onset conceals the progressive development of neurodegenerative diseases, also one of the highest incidence of disease in the elderly population.Clinical manifestations as follows: the cognition and memory dysfunction, activity of daily living been slow down, and have some mental symptoms and behavioral changes. The neurofibrillary tangles(NFT), age spots and particle vacuoles degeneration, etc. was the typical pathological features. At present, the cause of AD happened so far unknown, may be involved in pathogenesis of many factors, such as genetic factors, neurotransmitter, immune factors and environmental factors, etc.Opinions vary on the pathogenesis of AD, put forward various theories, of which "Aβtheory" as the mainstream theory.It thinks that because of the metabolic abnormalities, Aβ protein cannot be cleared in time, make its deposition in specific brain area, form the plaques, eventually lead to neuronal death, which cause the occurrence of AD.Hippocampus is the important part of the human brain, which belongs to the limbic system. It could strengthen the information of short-term memory to long-term memory. What’s more, it participates in space positioning. The hippocampus is the area of damage in AD. Presenting symptom of it was memorydysfunction and loss of direction of consciousness.Amyloid beta(Aβ), composed of 39-43 of amino acids, was the main component of senile plaques of the cerebral cortex.It wasthe substrateby the proteolytic enzyme of the amyloid precursor protein(APP).Among them, the most common was Aβ40 and Aβ42 clips.Although the Aβ40 was far more than Aβ42, the Aβ42 was more likely to forming amyloid protein.Therefore it had more toxic effects.PGRN(Progranulin)was a kind of secretory glycoprotein, which was encoded by chromosome 17 q21, composed of 593 amino acids. It plays an important role in embryonic development, tissue repair, tumor and inflammatory response, and other diseases.It was associated with a variety of nervous system diseases, such as frontotemporal dementia(FTD), AD, multiple sclerosis(MS) and ischemic cerebrovascular disease.Objective:Explore the expression of PGRN in hippocampus of AD model mice and the relationship between Aβ and it.Further confirmed that is involved in cell injury and apoptosis related mechanisms.Methods:1. Aβ1-42 was injected into the C57BL/6 mice’s hippocampus bilaterally to induce the model of Alzheimer’s disease.2. Using the HE staining and the Nissl’s staining to observethe morphology of hippocampal cells in different groups.3. Detecting the deposition of Aβin different groups by immunohistochemical.4. The contents of Aβin different groups via Elisa kit.5. Using immunohistochemistry and Western Blot method to detect PGRN in eachexpression in the hippocampus in mice.6. The use of immunohistochemistry and Western Blot method to detect apoptosis related gene Bax, Caspase 3, and the expression of Bcl- 2 within the different groups.Results:1.HE staining results showed that compared with the blank group, NS group have no much effect on cells in hippocampus; however, the model groups mainly caused the cell mutation in hippocampus dentate gyrus, such as hyperchromatic nuclei mainly for cells, nucleus pycnosis. The 1 d group was most pronounced in model group, with the passage of time, 7 d and 14 d groupsgradually reduced.2. Aβimmunohistochemistry and Elisa results indicated thatthe blank group and the NS group without Aβdeposition. What’s more, in the model group of hippocampus, the Aβexpression most in the 1 d group, 7 d group was less and the 14 d group was the least.The results have significant differences(p<0.001).3. In the immunohistochemistry and Western Blot of PGRN, it showed that small amounts of PGRN expression in blank group, but the expression of PGRN NS group obviously increased;In the model group, 1 group d PGRN express the most, with the passage of time, 7 d and 14 d groups of PGRN expression gradually reduced.The results have significant differences(p<0.001).4. Immunohistochemistry and Western Blot results of apoptosis related gene Bax, Caspase-3 demonstrated that the model group, expression at most in 1 d group, with the passage of time, 7 d and 14 d groups gradually reduced.The results have significant differences(p<0.05).5. Apoptosis related factor of the Bcl-2 immunohistochemistry and Western Blot results showed: in the model group, expression at least in 1 d group, with the passage of time, 7 d and 14 d groups highly expressed.The results have significant differences(p<0.05).Conclusion:1. The expression of PGRN was changed as the content of Aβ.They were positively correlated.2. The expression of PGRN appears positive correlation with the promotion of apoptosis proteins Bax and Caspase-3, nevertheless shows the negative correlation with the suppression of apoptosis protein Bcl-2.3. PGRN may participate in the pathological process of AD, and may be linked to the neuronal apoptosis mechanism exist in the process of AD pathology. It offers a new way for the research of AD. |
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