| Objectives: Alzheimer’s disease(AD) is a neurodegenerative disease ofthe central nervous system in the elderly, the major clinical manifestationsare memory and cognitive impairments, emotion, personality and behaviorchanges. With the development of society, the aging of the population hasbecome increasingly evident. It’s estimated that above the age of55, themorbidity of AD will double as the age increase every5years and above theage of85, nearly50%of the elderly have AD. The morbidity of AD willquadruple after2050, someone predicts. Vascular endothelial growth factor(VEGF) is one of the main angiogenesis prompting factors, secreted byvascular endothelial cells (vascular endothelial cells, VECs). It’s a highlyspecific endothelial cell mitogen, and also an effective angiogenesis andvascular permeabilitysexual inducible factor, which plays an important rolein both physiological and pathological processes. P38MAPK is one of themitogen activated protein kinase members, it vastly exists in mammaliancells and can be stimulated by hypoxia, ischemia, inflammatory factors,oxygen free radicals, endotoxin and so on. After being activated, it movesinto the cell’s nuclear to mediate inflammation, apoptosis and other effects.On the same time, P38MAPK can stimulate mass inflammatory cytokines,which can damage the neurons directly, inflammatory factors can stronglystimulate P38MAPK in return, thus forming an increasing positive feedbackpathway. As a result, the inflammatory response continues to be enlarged,leading to memory and cognition dysfunction. In recent years, many scholarsbelieve that numerous AD patients have vascular dysfunction and there is aclose link between cerebral ischemia and AD. Cerebral ischemia plays acatalytic role in the neurodegenerative process of AD. New vessels appearsafter injecting VEGF into AD rats’ brain tissue, this indicate that the exogenous VEGF can increase the number of new vessels greatly, improvethe blood supply of the ischemic tissue effectively and decrease hippocampaltissue’s injury largely so as to improve the AD rats’ learning and memoryability. Setting the function of vascular endothelial in AD rats as abreakthrough point, this study intends to observe the effect of Shengui YizhiFang on the expression of VEGF, P38MAPK and phosphorylated P38MAPKprotein in hippocampal area of AD model rats injected of Aβ1-42and toexplore the potential mechanism of AD, and the effect of Shengui YizhiFang on AD.Methods: Forty health male SD rats were randomly divided into fourgroups: the blank group, the control group, the high dose group and the lowdose group, the last two group were given Shengui Yizhi Fang. Each groupcontained10rats. The AD model group was established by injecting Aβ1-425ul into the rats’ bilateral hippocampus using stereotaxis instrument. Oneweek after modeling, detect the40rats’ learning and memory ability throughMorris water maze experiment. Two weeks after modeling, according to thelow dose group12.5kg/mg, the high dose group25mg/kg give the twogroups Shengui Yizhi Fang through lavage, while the control group was onlygive same volume physiological saline. Drug intervention last for4weeks,2times each day. Through the HE staining to observe the pyramidal cells’morphological changes in the rats’ hippocampal CA1area. Through theimmune histochemical method to detect the expression of VEGF in the samearea and extract total protein in hippocampus of rats at the same time.Through protein quantitative BCA method to measure the proteinconcentration. Through Western Blot method to detect the expression ofP38MAPK and phosphorylated P38MAPK.Results：1. The result of Morris water maze experiment showed that oneweek after modeling, each group’s latent period of escape was not same(F=102.332, P<0.05) and either dose the frequency of crossing platform.Compared with the blank group, other three group’s latent period of escapewas extended significantly and frequency of crossing platform was significantly less(P<0.05).2.HE staining: the pyramidal cells morphologicalwere in large quantity, regularly arranged, closely packed, evenly distributedand the cell morphology was normal in the rats’ hippocampal CA1area ofthe blank group. The pyramidal cells was obviously less, pyramidal cellswere in disorder, less quantity and scattered structure in the control group.Compared with the control group, the neuron’s number, shape and shapewere all recovered to different extent in drug intervention group, especiallyin the high dose group. The number of pyramidal cells increased than that inthe control group and cells were arranged in disorder, denser structure,forming a normal, uniform distribution.3.Expression of VEGF: There weresignificant difference during the four groups(F=105.859, P<0.05). Comparedwith the blank group, the expression of VEGF was less in the control group(P<0.05), but it was much higher than that in the drug interventiongroup(P<0.05). There was still difference between the high dose group andthe low dose group, the high dose group was higher than the low dose group(P<0.05).4.The expression of P38MAPK was no significant differenceduring the four groups(F=1.487, P>0.05), but the expression of phosphory-lated P38MAPK was difference (F=87.156, P<0.05). The control group wassignificantly higher than the blank group (P<0.05), the low dose group wasless than the control group(P<0.05), and the high dose group showedsignificant less than the low dose group (P<0.05).Conclusion:1. The rats were given bilateral hippocampus injection ofAβ1-42to induce AD, the40rats’ learning and memory ability changed so theAD model succeed.2. Shengui Yizhi Fang can improve AD rats’ learningand memory ability.3. The expression of phosphorylation P38MAPKincreased in the AD rats’ hippocampal area, but the expression of VEGF wasjust the opposite.4. Shengui Yizhi Fang can decrease the expression ofphosphorylated P38MAPK, but heighten the expression of VEGF. |
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