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Objective To investigate the effects of Epimedium ,Astragalus ,Radix Puerariae on DMT1 expression in the cere‐bral cortex of APPswe/PS1ΔE9 double transgenic mice model of AD .Methods A total of 60 specific‐pathogen‐free male APPswe/PS1ΔE9 double transgenic mice aged 6 months were equally and randomly assigned to model ,Epimedium ,Astragalus ,Radix puerari‐ae ,compound and DFO groups .An additional 10 6‐month‐old C57BL/6J mice served as negative control group .Using immunohisto‐chemistry and molecular biology methods to investigate the effects of a compound combining the effective components of Epimedi‐um ,Astragalus ,Radix puerariae on DMT1 expression in the cerebral cortex of APPswe/PS1ΔE9 double transgenic mice model of AD . Results Immunohistochemical staining results revealed that DM T 1 positive cell did not show in negative control group .DM T1 ex‐pression was higher in model group compared with the negative control group .DMT1 expression was lower in the compound and deferoxamine groups than in the model group .No significant difference was detected in DM T 1 expression between deferoxamine and compound groups .RT‐PCR ,Western blot and immunohistochemical staining results showed no significant difference .Conclusion These compounds can downregulate DMT1 expression and inhibit iron overload in the cerebral cortex of mice with Alzheimer′s dis‐ease ,reduce iron overload induced impairment of the central nervous system .
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Aim To observe the effects of effective fraction of Epimedium,Astragalus,Radix Puerariae on behavioral and pathological changes in a transgenic mouse model of Alzheimer’s disease.Methods Six-month-old APPswe /PS1 ΔE9 transgenic mice were ran-domly divided into 2 groups:model group and effective fraction group,1 0 mice each group.The mice in the effective fraction group were treated with the effective fraction of Astragalus,Radix Puerariae,Epimedium compound for 8 weeks.The C57BL/6J mice were used as negative control group.After 8 weeks,the learning and memory function were measured by Morris water maze,the pathological changes in brain tissue were ob-served by Modified Bielschowsky staining and Nissl 's staining.Results During place navigation trial,the escape latency in the APPswe /PS1 ΔE9 double transgenic model mice was longer than those of the mice of C57 (P 0.05 ). The Modified Bielschowsky staining shows that the neuron fibers of the cerebral cortex of APPswe /PS1 ΔE9 double transgenic mice were enlarged,swelling,and dense.There were senile plaques and nerve fiber tangles in the cerebral cortex of APPswe /PS1 ΔE9 double transgenic mice.The neuron fibers of mice in the effective fraction group were relieved;there was a small amount of senile plaque.The Nissl’s staining shows that the neurons of the cerebral cortex of APPswe /PS1 ΔE9 mice were edema, the number of cells were decreased.The mice in the effective fraction group were free of the disease.Con-clusion The double transgenic APPswe /PS1 ΔE9 mice of AD can simulate the specific pathogenesis of AD, which may be the efficient experimental animal model. The effective fraction of epimedium,astragalus and ra-dix puerariae may have a neuroprotective effect against AD via improving the learning and memory ability,and reduce the cerebral cortex nerve fiber tangles,senile plaques and neurons edema changes.
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Objective To investigate the effects of astragalus injection on the morphology and expression of Apaf-1 in hippocampal neurons after cerebral ischemia reperfusion in rats. Methods The male SD rats were randomly divided into 3 groups, sham-operated group, cerebral ischemia-reperfusion group (reperfusion group) and astragalus injection interven-tion group (experiment group). The global cerebral ischemia-reperfusion rat model was established by Pulsinelli four-vessel occlusion method. The astragalus injection group was intraperitoneally injected with astragalus 6 mL/kg, 30 mins before sur-gery and repeated every 24 h. Rat brains were removed 24 h after reperfusion in each group. HE staining was used to observe the pathological changes of the hippocampal neurons under the light microscope. The ultrastructural changes of hippocam-pal neurons were observed by transmission electron microscopy. Immunohistochemistry and Western blot methods were used to measure the expression of apoptotic protease activating factor-1(Apaf-1) protein. Results Compared with sham-operat-ed group, nuclear and mitochondrial damage was found in reperfusion group, and the expression of Apaf-1 protein increased obviously in hippocampus(Immunohistochemistry result:0.024 ± 0.001 vs 0.109 ± 0.011;Western blot result:0.270 ± 0.018 vs 0.894±0.072, P<0.01). Compared with reperfusion group, the damage in nuclear and mitochondria was relieved obviously in experiment group, and the expression of Apaf-1 protein in hippocampus was significantly decreased (Immunohistochemistry result:0.048±0.005;Western blot result:0.392±0.046, P<0.01). Conclusion Astragalus injection can reduce pathological damage of hippocampal neurons after cerebral ischemia and reperfusion in rats, and the mechanism is related with inhibiting of Apaf-1 protein.
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BACKGROUND:Alzheimer’s disease causes and pathogenesis remain unclear, which greatly restrict the screening of drugs. And the main reason is lack of suitable animal models. The developing transgenic animal technology al ows studying the role of certain pathogenic gene in vivo, and has regarded the ideal animal models for Alzheimer’s disease. OBJECTIVE:To summarize the research advance of Alzheimer’s disease transgenic animal models. METHODS:Using“Alzheimer’s disease, transgenic mouse, animal model, dementia”in Chinese and English as the key words, the first author retrieved PubMed and CNKI databases published before July 2013. Final y, 41 articles were included in result analysis. RESULTS AND CONCLUSION:The etiology of Alzheimer’s disease is diverse, and genetic factor is one important factor. The existing transgenic animal models of Alzheimer’s disease include single genetical y modified models, double genetical y modified models and multiple transgenic models. Single transgenic animal models can make a kind of mutated exogenous gene integrate into the genomes of animals by using recombinant DNA technology. This kind of models can be applied to only study one specific pathological change of Alzheimer’s disease. Double transgenic animal models can make two kinds of mutated exogenous gene integrate into the genomes of animals and simultaneously transfect animals by using recombinant DNA technology. This kind of models is closer to the pathological changes of Alzheimer’s disease than single transgenic animal models, but stil cannot simulate Alzheimer’s disease. Multiple genetical y modified models are obtained with different transgenic mice hybridization or several genes transfection, which are most similar to clinical process and pathological features of Alzheimer’s disease. However, this kind of models may develop a decline in consanguinity. Each kind of animal model has their advantages and shortcomings, and a better transgenic animal model is urgently needed to completely simulate pathological characteristics of Alzheimer’s disease.