| Alzheimer’s disease(AD) which is also called senile dementia is aSignificant source of disease resulted in dementia. As the acceleration ofpopulation and aging all over the world, AD has become the major globalpublic healthy problem. The patient’s quality of life have been seriouslyaffectted. The serious make the family and society’s burden much heavier notonly in spirit but also in economy. As the major disease of elderly dementia,AD is a neurodegenerative disease characterized by aggravated overallcognitive dysfunction and behavior damaged.It becomes a serious threat tohuman health with increasing incidence. In view of the current progress ofstudy, the research on drug of prevention and treatment focus on how to delaypatient’s death, prevent or delay partly the onset of the disease and improve thequality of patient’s life,and call for treatment with multi-factor andpersonalization.Butylphthalide (NBP) is a kind of chemical drug used for treatment ofacute ischemic stroke successfully, developed by our country withindependent intellectual property rights. Its chemical name is racemic-3-n-butyl phthalide. NBP can pass through the blood-brain barrier. Studies haveshown that the drugs could inhibit free radical and antioxidant enzymeactivities and so on. The aim of this experiment is to explore the effect ofButylphthalide(NBP) on learning and memory ability of rat induced byinjection amyloid (Aβ25-35) in bilateral hippocampus, as well as explore themechanism of NBP from oxidative stress so as to provide the experimentalbasis for the prevention and drug treatment for AD.Objective:To explore the effect of NBP on learning and damage in rat induced byAβ and the mechanism. Methods:1experiment group and management:40male Wistar rats were randomlydivided into five groups(control, model, NBP-L, NBP-H, VE, n=8). Thedistilled water was administered (ig, once for20d) to the control and themodel group, NBP (80mg/kg/d,120mg/kg/d, ig, once for20d) and VE(10mg/d)were administered in NBP-L, NBP-H and VE groups respectively. On theeighth day, saline was injected to bilateral hippocampus in the control group,and Aβ was injected to the other groups.One week after injection Aβ, Morriswater maze was performed for6d. Other2rats were killed after injection Aβfor3d to observe the needle path by cutting the fixed brain tissue continuallyinto30μm thick.2model preparation: colloidal state Aβ(5μl,10μg) was injected inhippocampus CA1region of rat(AP-3.5mm，ML±2mm，DV2.7mm) usingbrain stereotaxis technique.3Morris water maze test: One week after injection Aβ,Morris water mazewas performed twice a day lasting for6days to record the latency periodfinding the hidden platform. On the6th day, the platform was moved to recordthe times crossing the platform area, time staying in the platform quadrant,ratio of path in platform quadrant to the whole path during2Minutes4specimen management:2rats of each group were infused withparaformaldehyde, brain tissue was performed external fixation, paraffinimbedding, thionine Nissl body stain.5The serum preparation, detection of factors in serum, hippocampus,cortex: The blood was collected from heart in rat. Afterwards to detect theactivities of SOD, GSH-Px and the content of MDA in serum and freshhippocampus and cortex from5rats.6Statistical analysis：SPSS11.5software was used to make statisticalanalysis.Result:1Morris test result: the latency of control rats in3th,4th,5th,6th were24.62，18.01，14.25，10.30s respectively, and the latency of model in4d were significantly longer than those of control. Compared with model, the latencyof NBP-L, NBP-H and VE groups in4d were significantly decreased.In model group, times crossing the platform, time staying in the platformquadrant, ratio of path in platform quadrant to the whole path during2minwere significantly shorter than those in control(15.25，60.26s，62.33%).Compared with that of model those in NBP-L, NBP-H and VE groups weresignificantly increased.2Nissl stain: There were3-4layers cell in hippocampus CA1region incontrol, cell form were clear, integrity with dentrite; while in model, therewere an obvious neuron loss in CA1region, light nuclear staining withoutdentrite, and cell quantity of CA1region in model was significantly decreasedcompared with that of control. Compared with that of model the cellquantity were significantly increased in NBP-L, NBP-H and VE, the injurywas attenuated.Nissl body stain showed that in control group more cells in rat corticalneuronal morphology were clear, complete, clear nucleolus, Nissl stained dark,there were obvious protruding. Neuron loss in local regions of the cortexappeared in model group. Cell quantity was significantly decreased comparedwith that of control. The cell quantity were increased in NBP-L, NBP-H andVE groups compared with that of model.3SOD, GSH-Px, and MDA in rat serumThe activities of SOD(269.02)and GSH-Px(1907.03) in serum weresignificantly decreased in model compared with those of controlgroup(215.63，790.54). Those of NBP-L, NBP-H and VE groups weresignificantly increased compared with model group.The content of MDA (16.21nmol/ml) in serum was significantlyincreased in model compared with that of control group (8.73nmol/ml). Thecontent of MDA in NBP-L, NBP-H and VE groups were significantlydecreased compared with that of model group. Moreover, There are significantdifferences between NBP-L and NBP-H groups.4SOD, GSH-Px and MDA in rat hippocampus The activities of SOD(60.33) and GSH-Px(186.70) in hippocampus weresignificantly decreased in model group compared with those of control group(28.25，105.35). Compared with that of model group, the activities of SODwere significantly increased in NBP-L, NBP-H and VEgroups. And theactivity of GSH-Px was significantly increased in NBP-H than model group.The content of MDA in hippocampus was significantly increased inmodel(12.13) compared with that of control group(6.82), Compared with thatof model group, the content of MDA was significantly decreased in NBP-L(9.09), NBP-H(7.53)and VE group(9.29) groups.5SOD, GSH-Px and MDA in rat cortexThe activities of SOD(60.17) and GSH-Px(115.72) in cortex weresignificantly decreased in model group compared with those of control(30.81，69.98)group. The activities of SOD were significantly increased in NBP-L,NBP-H and VE groups when compared with that of model group. and theactivity of GSH-Px in NBP-H were significantly significantly higher than themodel group.The content of MDA in cortex was significantly increased in model(12.92)group compared with that of control(7.28) group. Compared with that ofmodel group, the content of MDA was significantly decreased in NBP-L,NBP-H and VE groups.Conclusion:1.It could be concluded that the injection of Aβ in hippocampus CA1region could cause severe damage in CA1region and cortex neuron, decreaselearning and memory ability. Administration of NBP-L, NBP-H and VEcould improve neuron structure of hippocampus, cortex, and improve learningand memory ability of rat. Butylphthalide has a beneficial brain protectionagainst the damage induced by Aβ and there was a dose-dependent.2. Injection of Aβ in hippocampus could decrease the activity of SOD andGSH-Px in serum, hippocampus and cortex of rats, Resulting increase theproduction of oxidative products, induce neuron damage. Administration ofButylphthalide could attenuate decreased enzyme activity induced by Aβ, decrease the production of oxidative products, attenuate neuron damage,protect neuron. This effect showed dose-dependent... |
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