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目的:研究黄芪甲苷(AS)对阿尔兹海默病(AD)脑中神经干细胞(NSC)增殖分化的影响。方法:分离胚胎大鼠神经干细胞,并以β淀粉样蛋白1-40(Aβ1-40)处理,MTT法检测AS对细胞增殖的影响;免疫细胞化学检测AS诱导神经干细胞分化的类型;Real-time PCR检测γ-分泌酶及Notch mRNA的表达。结果:高剂量AS能刺激NSC分化,中低剂量AS能够促进细胞增殖,减轻Aβ的细胞毒性作用。机制研究表明,AS既能抑制γ-分泌酶mRNA表达,也能促进Notch mRNA的表达。高剂量AS抑制γ-分泌酶mRNA表达的作用明显,中剂量AS则以促进Notch mRNA的表达为主。结论:高剂量AS能够通过抑制γ-分泌酶mRNA的表达,抑制Notch的激活从而诱导NSC分化。中剂量AS主要通过促进Notch的表达来促进干细胞增殖。
Objective: To investigate the effect of astragaloside IV on the proliferation and differentiation of neural stem cells (NSCs) in the brain of Alzheimer’s disease (AD). Methods: The neural stem cells of embryonic rats were isolated and treated with β-amyloid 1-40 (Aβ1-40). The effects of AS on cell proliferation were detected by MTT assay. The types of neural stem cells differentiated by AS were detected by immunocytochemistry. Real-time PCR detection of γ-secretase and Notch mRNA expression. Results: High-dose AS stimulated NSC differentiation. Low- and medium-dose AS could promote cell proliferation and alleviate the cytotoxic effect of Aβ. Mechanistic studies have shown that AS can both inhibit γ-secretase mRNA expression, but also promote Notch mRNA expression. The effect of high dose AS on inhibiting γ-secretase mRNA expression was obvious. The middle-dose AS promoted the expression of Notch mRNA. Conclusion: High-dose AS can induce NSC differentiation by inhibiting the expression of γ-secretase mRNA and inhibiting the activation of Notch. Mid-dose AS promotes stem cell proliferation mainly by promoting the expression of Notch.