调心方有效部位对类AD大鼠脑组织凋亡信号转导分子Caspase-3及凋亡相关基因bcl-2、bax mRNA表达的影响

目的研究调心方有效部位（TX0201）对Aβ25-35所致类AD模型大鼠脑组织凋亡相关基因调节作用机制的异同。方法采用双侧杏仁核注射Aβ25-35造成类AD大鼠模型，观察大鼠Morris水迷宫空间记忆能力，并分别通过RTPCR和免疫组化方法研究类AD大鼠神经元细胞凋亡相关基因bax、bcl-2 mRNA，特异的凋亡信号转导分子Caspase-3和A8阳性神经元变化以及TX0201的影响。结果类AD模型大鼠Morris水迷宫测试出现空间记忆能力下降，App695 mRNA表达提高，Caspase-3和bax／bcl-2上升。TX0201能有效控制以上病理变化。结论TX0201提高模型大鼠定向学习记忆能力，可能通过降低bax／bcl-2、下调Caspase-3而减轻神经细胞凋亡而发挥作用。提示通过有效调节神经元凋亡相关基因是TX0201的重要作用机制之一。

Effect of TX0201 on Expression of the Apoptosis Signal Transduction Molecule Caspase-3 and Apoptosis Associated Genes bcl-2 and bax Mrna in Brain Tissue of Rat Analogue Model of Alzheimer's Disease

OBJECTIVE: To study the mechanism of TX0201, an effective fraction extracted from Tiaoxin recipe in regulating apoptosis associated genes in brain tissue of rat analogue model of Alzheimer's disease (AD) induced by beta-amyloid protein 25-35 (Abeta 25-35). METHODS: The model of AD was induced by bilateral amygdala injection of Abeta 25-35 to study the spatial memory capacity using Morris water maze test, and by means of RT-PCR and immunohistochemistry assay, the expressions of beta-amyloid precursor protein (APP), apoptosis correlative genes (bcl-2, bax), and apoptosis signal transduction molecule (Caspase-3) in the brain, and the effect of TX0201 on expressions of these genes were examined. RESULTS: In AD model group, the spatial capacity was damaged significantly. Caspase-3 and the expression of APP mRNA and bax/bcl-2 mRNA were increased in the cortex and hippocampus; TX0201 ameliorated all the pathologic changes mentioned above. CONCLUSION: TX0201 could improve the oriented learning and memory capacity in AD rats by decreasing bax/bcl-2 and down-regulating Caspase-3 to reduce neurocyte apoptosis, suggesting that effective regulation of neuron apoptosis associated genes may be one of the mechanisms of TX0201.