| Background and ObjectiveAlzheimer disease (AD) is a progressively disease of unknown cause charactered by progressively reduced cognitive funcition. Scientists have pointed that not only the synapse's numbers and structure altered but also the levels of expression of the functional proteins (postsynPatie density protein 95), Nerve growth factor,Tyrosine receptor and the important nuclear factor kinase Extracellular signal regulatory protein kinase which may play an important role in the synapse's survival changed in AD patients. What'more, we still havn't found accurately effective treatment to it. so there are some theoretical significance to study on the neuroprotective effects of synapse of AD. Traditional Chinese medicine have found that some Chinese medicines may have curative effects to the intelligence of AD patients. We used shou er zhi capsules which have the main function of invigorating the kidney, eliminating phlegm,and activating blood flow to the treatment of Alzheimer disease and found they have accurately curative effects on AD patients. Previous researches have found that shou er zhi capsules have mechanisms on improving the intelligence of AD rat's in many aspects. But shou er zhi capsules's contribution to the neuroprotective effects of synapse is still untouched. This research state the relationship between AD and impairments of synapses and the possible mechanisms about shou er zhi capsules's effect to this neuroprotective effects through observing the changes of behavior of the AD rats, ultramicrostructure of synapses, the levels of expression of PSD-95,NGF, TrkA,ERK1 and ERK2 and the shou er zhi capsules's influence to these indicators.MethodForty Sprague-Dawley(SD) rats were divided into four groups randomly:sham-operated group, model group, Donepezil group and shou er zhi group. AD animal model was duplicated by injected 25-35 fragments of Aβinto the double hippocampus of rat's. Three days later, shou er zhi groups were given shou er zhi.Donepezil groups were given Donepezi. The sham-operated group and model group were treated with equale Sodium Chloride respectively.28 days later, Behavioral changes were inspected to determine the learning and memory of AD rats through Morris water maze test; the neuronal morphous in CA1 of the hippocampus were viewed through HE stain; the ultramicrostructure of synapse in CA1 of the hippocampus were observed by using transmission electron microscope and the parameters of the synaptic interface in area CA1 of the hippocampus were analyzed through image analyzer. The levels of expression of PSD-95,NGF,TrkA,ERK1,ERK2 in area CA1 of the hippocampus was determined by immunity tissue method; RT-PCR was used to measured the levels of expression of PSD-95mRNA, NGF mRNA, TrkA mRNA ERK1 mRNA andERK2 mRNA in the hippocampus.Result1. shou er zhi can improve the intelligence of AD rats. In place navigation test, compared with the sham-operated group, the escape latency was significantly longer in the model group(P<0.01); In shou er zhi group and Donepezil group the the escape latency were significantly shorter than that in the model group (P<0.01). In spatial probe test, the test showed that swimming time in the platform of first quadrant was significantly shorter in model group than that in the sham-operated group (P<0.01), in shou er zhi groups and Donepezil groups, swimming time in the platform of first quadrant were significantly longer than that in the model group (P<0.05),and there was no significantly difference between Donepezil group and shou er zhi groups.2. Compared with the sham-operated group, the numbers of neurons in the hippocampal CA1 areas of the rats in model group reduced remark-ably, the neurons arranged irregularerly, the impairments of the structure of synapse in CA1 area are especially obvious. But in shou er zhi group and Donepezil group, the numbers obviously increased, the distribution became regularer and the impairments reduced apparently.3. Compared with the sham-operated group,the width of synaptic cleft in the hippocampal CA1 areas of the rats in model group was remarkably increased, the thickness of PSD reduced apparently (P<0.01). But shou er zhi group and Donepezil group can reverse these pathological changes of synaptic interface significantly (P<0.01); and there was no difference between Donepezil group and shou er zhi groups.4. Compared with the sham-operated group, The expression of PSD-95,TrKA,ERK1,ERK2 in the hippocampal CA1 area of the rats in model group were prominently decreased(P<0.01); but in shou er zhi group and donepezil group,the expression were obviously increased (P<0.05/P<0.01); and there was no difference between Donepezil group and shou er zhi groups.5. Compared with the sham-operated group, The expression of PSD-95 mRNA. TrKA mRNA,ERK1 mRNA,ERK2 mRNA in the hippocampal of the rats in model group were prominently decreased(P<0.01); but in shou er zhi group and donepezil group,the expression were obviously increased(P<0.05/P<0.01); and there was no difference between Donepezil group and shou er zhi groups.Conclusion1. We injected Aβ25-35 into the rat's hippocampus in order to duplicated the model of AD. This model can simulate the behavior and pathological features of AD and had a better reproducibility and stabilization. This model was an ideal model for research in AD.2. AD models induced by Aβ25-35 existed the damage of synapses and the mechanism is presumably related to inducing the structural impairment of synapse, reducing the expression of PSD-95,TrKA,ERK1,ERK2 in the hippocampus apparently and obstacling neuronal survival signal transduction pathways.3. Shou er zhi has a protective effect on neurons and synapses damaged by Aβ25-35 and the mechanism is presumably related to relieving the damage of the synapses of strucyure in area CA1 of the hippocampal of the rats in model group.4. Shou er zhi has protective effect on neurons and synapses impaired by Aβ25-35 and the presumably mechanism is related to increasing the expression of PSD-95,TrKA,ERK1,ERK2 in area CA1 of the hippocampal of the rats in model group, stimulating neuronal survival signal transduction pathways. |
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