阿魏酸钠通过SIRT1/FOXO3A改善血管性痴呆大鼠学习记忆障碍的机制研究

Mechanism study of sodium ferulate in improving learning and memory in vascular dementia rats via SIRT1/FOXO3A pathway

目的探究阿魏酸钠在血管性痴呆(vascular dementia,VD)大鼠中的神经保护作用及其对前额叶皮质沉默信息调节因子1(silent information regulator 1,SRIT1)和叉头框转录因子O3A(forkhead box transcription factor O3A,FOXO3A)表达的影响。方法将32只雄性SD大鼠随机分成4组,每组8只。模型组和阿魏酸钠组大鼠行双侧颈总动脉栓塞;假手术组进行相同的手术操作,但不做结扎处理;正常组不做处理。阿魏酸钠组连续4周灌胃阿魏酸钠溶液(100 mg/kg),其余3组接受相同体积的生理盐水灌胃。通过Morris水迷宫、尼氏染色、Western Blot和免疫组织化学染色法观察比较各组大鼠行为学、细胞形态及SIRT1和FOXO3A蛋白的表达情况。结果正常组和假手术组神经元呈现较完整的形态结构。相较于正常组,模型组大鼠逃避潜伏期显著延长、穿越平台次数明显减少(P<0.05),细胞核固缩,SIRT1表达水平显著下降(P<0.05),FOXO3A表达显著上升(P<0.05);与模型组相比,阿魏酸钠组细胞形态得以改善,逃避潜伏期和FOXO3A蛋白表达均降低(P<0.05),穿台次数和SIRT1蛋白表达水平均升高(P<0.05)。结论阿魏酸钠通过调节SIRT1/FOXO3A改善大鼠学习记忆能力,为VD治疗提供了一定的研究基础。

Objective To observe the neuroprotective effects of sodium ferulate on the prefrontal cortex of rats with vascular dementia(VD)and to explore its impact on the expression of SIRT1 and FOXO3A proteins.Methods Thirty-two male Sprague-Dawley(SD)rats were randomly divided into four groups,with 8 rats in each group.The model group and the sodium ferulate group underwent bilateral common carotid artery embolization(BCCAO)to induce VD,the sham group underwent the same surgical procedure without ligation,and the normal group received no treatment.The sodium ferulate group was administered sodium ferulate solution(100 mg/kg)intragastrically for four weeks,while the other three groups received an equivalent volume of saline by gavage.The behavioral,cellular morphology,and protein expression levels of SIRT1 and FOXO3A were analyzed using the Morris water maze,Nissl staining,Western Blotting,and immunohistochemical staining.Results Neurons in the normal and sham groups maintained intact morphological structures.In contrast to the normal group,the model group demonstrated significantly prolonged escape latency,reduced platform crossings(P<0.05),nuclear shrinkage,a significantly decreased expression of SIRT1(P<0.05),and a notable increase in FOXO3A expression(P<0.05).In comparison to the model group,the sodium ferulate group exhibited enhanced cortical cell morphology,decreased escape latency and FOXO3A protein expression(P<0.05),and increased platform crossings and SIRT1 protein expression(P<0.05).Conclusion Sodium ferulate enhances learning and memory abilities in VD rats by regulating SIRT1/FOXO3A pathway,providing a research foundation for the treatment of VD.