The Protective Effects Of β-aescinate On Cerebral Inflammatory Damage Of Alzheimer's Disease Model Rats

Alzheimer's disease (AD) is a degenerative disorder of thebrain characterized by progressive dementia. Its pathologicalfeatures are extracellular senile plaque (SP) formed by thedeposition of the β -amyloid (A β ), degenerating neurons,neurofilament tangle (NFT) and the presence of numerousactivated astrocytes and microglias. All of the pathologicalchanges are related to Aβ according to the recent notion andglial activation as well as the immune and inflammatory responseare invoved in the pathogenesis of AD. Now,cholinesterase-inhibitors (ChEIs) is applied widely as thepharmacologic treatments for AD, which improve the level ofcognitive function but not provide neural protective effect byenhancing the activity of the synaptic cleft. This therapy couldonly improve some symptoms. Recently, some study about theinflammatory mechanism of AD provide a better therapeuticapproach which aims at the causation not the symptom. We usedthe animal model of AD by stereotaxic damage of CA1 area ofleft rat hippocampus using aggressive A β 1-40 in thisexperiment.And a group model rats were treated byintroperitoneal injection of β-aescinate.Two weeks later, weobserved the changes of their memory and the hippocampuspathological abnormalities. we observed the prevention ofβ-aescinate to the Aβ-injured rats, try to explain its preventivemechanism and provide the experimental evidence for theβ-aescinate used in clinics.Ⅰ. The establishment of the rat model of inflammatorypathology for ADAβis the core of SP, which is the major pathological featureof AD, and related to the other pathological hallmark such as NFT,degenerating neurons and glial activation;The hippocampus isthe most vulnerable area, and is highly related to the ability ofstudy and memory, especially recent memory. So the rat model ofhippocampal CA1 region damage by Aβ is a good choice tostudy the pathological and behavioral changes in AD. Westereotaxically damaged hippocampal CA1 region (3.0mm behindthe anterior fontanelle, 2.2mm to the left of the sagittal suture,2.8mm under the dura mater) of AD rat using Aβ1-40 according to"The stereotaxic atlas of rat brain", and observed the changes ofmemory using morris test and the hippocampus pathologicalabnornalities.The results showed: (1) The model had such advantages asexact localization, high success rate, and good repetition, etc. (2)Morris test: AD rat showed significant decreases in the time ofmemory recovery (p<0.05). (3)Numerous gliacytes could be seenbeside the needle trace in the Aβgroup which imatated thestructure of SP.The results suggested: we have successfully established therat model of hippocampal CA1 region damaged by Aβ, whichpartly imitated the behavioral and pathological changes ofAlzheimer disease, such as the memory dysfunction, thedeposition of Aβ and neuron loss etc. It is a satisfactory modeldirected against the mechaniam of Aβ neurotoxity and itspharmaceutical therapy.Ⅱ. Effect of β-aescinate on hippocampal gliacytes of the ADmodel ratsThe gliacytes compose the microcondition of central nervoussystem. Activaed gliacytes are important for pathological changesof AD.The quantity of microglia cells and astrocytes activatedsuccessionally increases on hippocampus of AD. They secretemany cytokines such as nitrous oxide, oxygenous free radical etc.We study the changes of the hippocampal gliacytes of AD modelrats which were injected β-aescinate by immunohistochemicalmethods.The result showed: numerous gliacytes were observed inhippocampus in Aβ group compared with those in pseudooperation group, significantly different from those in A β+β-aescinate group (p<0.05).The result suggested: A β 1-40 can activate gliacytes.β-aescinate can restrain the activation of hippocampal gliacytesevidently, so it may provide some protective effects for cerebralinflammatory damage of alzheimer's disease model rats.Ⅲ. Effect of β-aescinate on quantity of cytokines in thehippocampus of the AD model ratsCytokine is the medium between central nuervous systemwith immune system. Activated neuroglias can secret a largenumber of cytokines. While the excessive expression and releaseof interleukin-1 is the first step. Interleukin-1 can not onlypromote neuroglials to express cytokines but also induce theproduction of alexin,oxygenous free radical,nitrous oxide,S100β,β-APP etc. these molecule promotes the exudation of otherinflammatory molecule by acting on neuroglias or nervecells,which accelerates the production of chronic inflammatoryreaction and the persistent increase of inflammatoryproductions.We studied the changes of quantity of IL-1 and TNFby immunohistochemical method in our experiment.The results suggested that the quantity of IL-1 and TNF inthe left hippocampus is more in Aβ group compared with thosein pseudo operation group, significantly different from those in Aβ+β-aescinate group (p<0.05).The result suggested:the injection of A β into sinistralhippocampus leaded the expression of a large number ofcytokines. β-aescinate can reduce the quantity of IL-1 and TNF inthe left hippocampus of model rats, which provide protection forcerebral inflammatory damage of alzheimer's disease model ratsin a certain extent.