| The protection of dexamethasone on cerebral inflammatorydamage in dementia rat models. Recently, as continued in-depth studying of Alzheimer's disease.In Alzheimer's pathogenesis, it's become more and more importantthat the cerebral inflammatory damage by β-amyloid. Its pathologicalfeatures are extracellular senile plaque (SP) formed by the depositionof theβ-amyloid (Aβ), degenerating neurons,neurofilament tangle(NFT). Aβ as the main part of SP, is consinded that it can induce thedamage of neuron and the decline of cognition function. All of thepathological changes are related to Aβ according to the recent notionand glial activation as well as the immune and inflammatory responseare invoved in the pathogenesis of Alzheimer's disease. And thepresence of numerous activated astrocytes and microglia are theimportant immunocyte. 1. The establishment of the rat model of hippocampal CA1region damage by Aβ. Our investigation used the animal model of AD by stereotaxicdamage of CA1 area of left rat hippocampus using aggressive Aβ1-40in this experiment. We observed the changes of their memory andthe hippocampus pathological abnormalities, and the activity changesof microglia and astrocyte. Mensurating the inflammation reaction inCA1 area of left rat hippocampus by immunohistochenmical assay.And at the same time, we observed the prevention of dexamethasoneto the Aβ1-40injured rats, try to explain its preventive mechanismand provide the experimental evidence for the glucocorticoid used inclinics. The hippocampus is the most vulnerable area, and is highlyrelated to the ability of study and memory, especially recent memory.So the rat model of hippocampal CA1 region damage by Aβ is a goodchoice to study the pathological and behavioral changes inducing byAβ in AD. We stereotaxically damaged hippocampal CA1 region(3.0mm behind the anterior fontanelle, 2.2mm to the left of the sagittalsuture, 2.8mm under the dura mater) of AD rat using Aβ1-40accordingto "The stereotaxic atlas of rat brain", and observed the changes ofmemory using morris test and the hippocampus pathologicalabnornalities. The results showed: (1) The model such AD vantagesas exact localization, high success rate, and good repetition. (2) morristest: AD rat showed significant decreases in the time of memoryrecovery (p<0.05). (3) Mild gliosis could be seen beside the needletrace in the saline group, there were not neuronal apoptosis in thecortex and hippocampus with HE staining.Meanwhile, in the Aβ group,the neuron number in hippocampus was smaller than in the salinegroup, the degenerated neurons and gliosis were seen and there werefew solitary shrunken neurons in hippocampus. (4) Neuro expressionof IL-1βand TNF-αin the cortex and hippocampus is activation withimmunohistochenmical assay, prove that Aβcan activat astrocyte andmicroglia, induce the excess expression of inflammatory factors andinflammatory reaction.The results suggested: we have successfully established the ratmodel of hippocampal CA1 region damaged by A β, which partlyimitated the behavioral and pathological changes of Alzheimer'sdisease, such as the memory dysfunction, the deposition of Aβ andneuron loss. It proved the condition easy to control in space and timein studying the mechanism and of damage induced by Aβ, and is asatisfactory model directed against the mechaniam of Aβ neurotoxityand its pharmaceutical therapy.2. The effects of dexamethasone on the rat model of hippocampalCA1 region damage by β-amyloid injection Dexamethasone belongsto glucocorticoids, has the glucocorticoids's anti-inflammatorycharacter, Mosts glucocorticoids make functions through thecombination of glucocorticoids' receptors, To achieve the target by thecomplex signal transduction, the increase or decrease target geneexpression. Our investigation used the animal model of AD bystereotaxic damage of CA1 area of left rat hippocampus usingaggressive Aβ1-40 in this experiment. And at the same time, weobserved the prevention of dexamethasone to the Aβ-injured rats, tryto explain its preventive mechanism and provide the experimentalevidence for the glucocorticoid used in clinics.The results showed: Our study found that in the A β+dexamethasone group, the neuro lost is more alleviately than Aβgroup and Aβ+ brine group, Statistical results (P<0.05). Significantlydifference.The results suggested: The results showed that in a certainextent, dexamethasone can protecte the neuro in the rat model ofhippocampal CA1 region damage by by β-amyloid injection. Notehere dexamethasone play a positive role in the conditions of the pilotmodel by alleviating Aβ-induced nerve damage.1. The effects of dexamethasone on the rat model of hippocampalCA1 region damage by by β-amyloid injection.Aggressive A β 1-40activate microglia. Microglia widelydistributed in the central nervous system, accounting for a total ofmicroglia 1/4. Astrocyte is the most widely distributed of centralnervous tissue, its role to protect nutrition, and it is important immunecells secreted in Alzheimer's disease it participated in many importantinflammation response process. Through immunohistochenmicalassay observe the changes of microglia and astrocyte of the AD rat bydexamethasone intervention in this experiment. To discuss thedexamethasone possible mechanisms of inhibit inflammationresponse.The results showed: The number of activation microglia in theAβ+ dexamethasone group is significantly lessen than it in the Aβ+brine group. And astrocyte body smaller, synapse shorter, reducing thenumber. From the statistical analysis P<0.05. Significantly difference.The results suggested: Microglia and astrocyte are participate inthe inflammation response process. The inhibition of dexamethasoneto the activation microglia and astrocyte is significantly. Thisexperiment suggested inhibition activation gliosis may be one of theway that dexamethasone protect neuro. Microglia response in acuteinflammation played a role in the protection of nerve cells , However,in long-term incentives with A β deposition and microgliafactor-secretion of inflammation mutual feedback ,microglia is atoxicity role in promoting the degenerative neuros. The statisticalresults show the inhibition of dexamethasone to the activationmicroglia and astrocyte is significantly. Accordingly, dexamethasonemay be inferred through the active suppression of gliosis way off isfeedback cycle. Thereby inhibition the activation of gliosis andprotecting the nerve cell.1. The effects of dexamethasone on the pro-inflammatory factorsin rat model of hippocampal CA1 region damage by by β-amyloidinjectionTNF-α and IL-1βare important cell factors in the inflammationresponse, both cellular immunity and humoral immunity. TNF-αprimarily secretion by activity microglia. A study has shown Aβcandirectly activate microglia release TNF-α,both them synergies caninduce astrocyte release of NO, damage neuros. Throughimmunohistochenmical assay observe the changes of expressionTNF-α and IL-1βof the AD rat by dexamethasone intervention in thisexperiment. Discussing the possible fuctions of pro-inflammatoryfactors in the process of AD, and the dexamethasone's effection of thepro-inflammatory factors' expression.The results showed: The expression IL-1βor TNF-α cells in theAβgroup are significantly more than in the sham operation group,P<0.05,the results of statistical analysis showed that there weresignificant differences . The expression IL-1βor TNF-α cells in the Aβ+ dexamethasone group is significantly less than in the Aβ+ brinegroup, P<0.05, significantly differences. The masculine cells in the Aβgroup aren't significantly more than in the Aβ+ brine group, P>0.05.The results suggested: Accordingly, we conclude that aggressiveAβ1-40activate expression the IL-1βor TNF-α cells. It's proved that inthe process of AD inflammation factors involved. It's proved thatdexamethasone can inhibit the secretion of TNF-α and IL-1β. This isconsensus of the related research reports or conclusions of the current.The facts support the hypothesis of the inflammation responsemechanisms in AD.
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