益肾化浊方调控MAPK/ERK信号通路治疗阿尔茨海默病的作用机制研究

Mechanism of Yishen Huazhuo Formula in treating Alzheimer’s disease via regulating MAPK/ERK signaling pathway

关键词:  阿尔茨海默病  益肾化浊方  认知功能  突触形态学  MAPK/ERK信号通路

Key words:  Alzheimer’s disease  Yishen Huazhuo Formula  cognitive function  synaptic morphology  MAPK/ERK signaling pathway

摘要:

[目的] 围绕丝裂原活化蛋白激酶（MAPK）/细胞外信号调节激酶（ERK）信号通路探讨益肾化浊方（YSHZD）治疗阿尔茨海默病（AD）的作用机制。[方法] 40只雄性SD大鼠分成假手术组、模型组、YSHZD组、安理申组，每组10只。通过侧脑室注射β-淀粉样蛋白（Aβ）_25-35建立大鼠AD模型，水迷宫实验评价各组大鼠的学习记忆能力，尼氏（Nissl）染色和透视电镜分别观察大鼠海马区神经细胞凋亡情况及神经元突触形态学，蛋白免疫印迹（Western blot）实验检测大鼠海马区丝裂原活化蛋白激酶（MAPK）/细胞外信号调节激酶（ERK）信号通路相关蛋白的表达。[结果] YSHZD可以改善AD大鼠的认知功能，并且能够改善神经细胞存活率，保护神经元突触形态，还可以不同程度地促进蛋白激酶C（PKC）和B-Raf蛋白表达，而抑制Ras、Raf1、ERK蛋白表达。[结论] YSHZD可以通过调节MAPK/ERK信号通路提高神经细胞存活率，保护神经元突触，从而显著改善AD大鼠的认知功能障碍。

Abstract:

[Objective] To investigate the mechanism of Yishen Huazhuo Formula（YSHZD） in treating Alzheimer’s disease（AD） through the mitogen-activated protein kinase（MAPK）/extracellular signal-regulated kinase（ERK） signaling pathway. [Methods] Forty male SD rats were randomly divided into sham-operated group（Sham），model group（Model），YSHZD group，and Aricept group（n=10 per group）. The AD model was established by intracerebro- ventricular injection of β-amyloid peptide（Aβ_25-35）. Morris water maze test was performed to evaluate learning and memory abilities. Nissl staining and transmission electron microscopy（TEM） were used to observe neuronal apoptosis and synaptic morphology in the hippocampus，respectively. Western blot was employed to detect the expression of MAPK/ERK pathway-related proteins. [Results] YSHZD significantly improved cognitive function in AD rats，enhanced neuronal survival rate，and protected synaptic ultrastructure. Furthermore，it upregulated the expression of protein kinase C（PKC） and B-Raf proteins，while downregulating Ras，Raf1，and ERK protein levels. [Conclusion] YSHZD ameliorates cognitive dysfunction in AD rats by regulating the MAPK/ERK signaling pathway，thereby promoting neuronal survival and synaptic integrity.