Laboratory of Stem Cells and Tissue Engineering, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China.
Laboratory of Stem Cells and Tissue Engineering, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China.
Neurochem Int. 2019 Jan;122:149-156. doi: 10.1016/j.neuint.2018.09.003. Epub 2018 Sep 7.
The incidence of neurodegenerative diseases is severely increasing with the aging. It has been proposed that NSCs (neural stem cells) help to control aging, but the mechanisms responsible remain unclear. Angelica polysaccharide is an active ingredient of Angelica sinensis in traditional Chinese medicine, which possesses versatile pharmacological activities including anti-oxidative and anti-aging effects. In this study, D-gal (D-galactose) was used to construct an aging model of Nestin-GFP transgenic mice brain tissues and NSCs. Mouse model was subcutaneously injected with D-gal, as we observed that mice consistently displayed acceleration of aging-like behavior change, energy metabolism decreased, the expression of aging-related genes was up-regulated. Conversely, aging retardation was achieved in Nestin-GFP mice Induced by D-gal that was locally injected with ASP (Angelica polysaccharide). Mechanistically, we isolated and cultured NSCs in vitro. ASP protected NSCs by increasing the cell proliferation; decreasing the number of SA-β-gal stained neurons; increasing the activity of SOD(superoxide dismutase) and T-AOC(total antioxidant capacity), decreasing the content of MDA(malondialdehyde); decreasing the levels of IL-1b,IL-6,TNF-a and ROS; and down-regulated the expression of cellular senescence associated genes p53, p21 in the aging NSCs. In conclusion, ASP can delay aging speed by protecting NSCs and promote neurogenesis by enhancing the antioxidant and anti-inflammatory capacity, up-regulation of p53/p21 signaling pathway. As to provide theoretical basis for treatment for brain aging related diseases, add new scientific connotation for "qi and blood theory" and "supplement blood and delay aging" of Traditional Chinese Medicine.
神经退行性疾病的发病率随着老龄化的加剧而严重增加。有人提出神经干细胞(NSCs)有助于控制衰老,但负责的机制仍不清楚。当归多糖是中药当归的一种活性成分,具有多种药理活性,包括抗氧化和抗衰老作用。在这项研究中,D-半乳糖(D-galactose)被用于构建 Nestin-GFP 转基因小鼠脑组织和 NSCs 的衰老模型。通过皮下注射 D-gal 观察到,小鼠持续表现出加速衰老样行为改变、能量代谢降低、衰老相关基因表达上调,从而构建了衰老模型。相反,局部注射 ASP(当归多糖)可使 Nestin-GFP 小鼠的衰老延缓。从机制上讲,我们在体外分离和培养了 NSCs。ASP 通过增加细胞增殖、减少 SA-β-gal 染色神经元的数量、增加 SOD(超氧化物歧化酶)和 T-AOC(总抗氧化能力)的活性、降低 MDA(丙二醛)的含量、降低 IL-1b、IL-6、TNF-a 和 ROS 的水平、下调衰老 NSCs 中细胞衰老相关基因 p53、p21 的表达来保护 NSCs。总之,ASP 通过保护 NSCs 来延缓衰老速度,并通过增强抗氧化和抗炎能力、上调 p53/p21 信号通路来促进神经发生。为治疗与大脑衰老相关的疾病提供了理论依据,为中医的“气血理论”和“补血延缓衰老”增添了新的科学内涵。