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人参皂苷 Rg1 通过抑制线粒体途径介导的细胞凋亡和激活衰老相关蛋白 3(SIRT3)/超氧化物歧化酶 2(SOD2)通路在衰老大鼠模型 Sca-1+造血干细胞/祖细胞(HSC/HPC)中发挥抗衰老作用。

Ginsenoside Rg1 Performs Anti-Aging Functions by Suppressing Mitochondrial Pathway-Mediated Apoptosis and Activating Sirtuin 3 (SIRT3)/Superoxide Dismutase 2 (SOD2) Pathway in Sca-1⁺ HSC/HPC Cells of an Aging Rat Model.

机构信息

Department of Histology and Embryology, Dali University, Key Laboratory of Cell Biology in Yunnan Province, Dali, Yunnan, China (mainland).

Stem Cell and Tissue Engineering Laboratory, Department of Histology and Embryology, Chongqing Medical University, Chongqing, China (mainland).

出版信息

Med Sci Monit. 2020 Apr 7;26:e920666. doi: 10.12659/MSM.920666.

Abstract

BACKGROUND Aging is characterized by progressive deterioration in metabolic and physiological process. The present research assessed the antagonistic effects and mechanisms of Ginsenoside Rg1 (Rg1) on aging of HSCs/HPCs. MATERIAL AND METHODS Fifty male Sprague-Dawley (SD) rats were treated and divided into the following groups: Control (n=10), Model (n=10, treated with D-galactose, as aging model), Rg1 Control (n=10), Rg1 treatment (n=10), and Rg1 prevention (n=10). An aging rat model was established by subcutaneous injection with D-gal. HSC/HPC cells were stained using SA-ß-Gal staining. HSC/HPC cells were examined using flow cytometry assay. CFU-mix assay, with a few modifications, was performed. Cleaved caspase-3, B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) were examined using qRT-PCR. Sirtuin 3 (SIRT3) and superoxide dismutase 2 (SOD2) expression was determined using Western blot assay and qRT-PCR. RESULTS Rg1 (treatment and prevention group) significantly decreased SA-ß-Gal-positive staining in Sca-1⁺ HSC/HPC cells compared to that of the D-gal model (p<0.05). Rg1 significantly enhanced formation capacity of CFU-Mix compared to the D-gal model (p<0.05) in Sca-1⁺ HSC/HPC cells. Rg1 significantly reduced G0/G1 phase of Sca-1⁺ HSC/HPC cells compared to that of the D-gal model (p<0.05). Rg1 significantly decreased cleaved caspase 3 and Bax expression, and increased Bcl-2 expression compared to the D-gal model (p<0.05). Rg1 treatment remarkably upregulated expressions of SIRT3 and SOD2 compared to that of the D-gal model group (p<0.05). CONCLUSIONS Rg1 conducted functions of anti-aging in Sca-1⁺ HSC/HPC cells in the D-gal-induced aging model by inhibiting mitochondrial pathway-mediated apoptosis and activating the SIRT3/SOD2 signaling pathway.

摘要

背景

衰老是代谢和生理过程逐渐恶化的特征。本研究评估了人参皂苷 Rg1(Rg1)对造血干细胞/祖细胞(HSCs/HPCs)衰老的拮抗作用及其机制。

材料和方法

50 只雄性 Sprague-Dawley(SD)大鼠经处理后分为以下几组:对照组(n=10)、模型组(n=10,用 D-半乳糖处理,作为衰老模型)、Rg1 对照组(n=10)、Rg1 治疗组(n=10)和 Rg1 预防组(n=10)。通过皮下注射 D-半乳糖建立衰老大鼠模型。用 SA-β-半乳糖染色法对 HSC/HPC 细胞进行染色。采用流式细胞术检测 HSC/HPC 细胞。对 CFU-mix 进行改良后进行检测。采用 qRT-PCR 检测裂解的半胱天冬氨酸蛋白酶 3(caspase-3)、B 细胞淋巴瘤-2(Bcl-2)和 Bcl-2 相关 X 蛋白(Bax)。采用 Western blot 法和 qRT-PCR 法检测 Sirtuin 3(SIRT3)和超氧化物歧化酶 2(SOD2)的表达。

结果

与 D-半乳糖模型组相比,Rg1(治疗和预防组)可显著降低 Sca-1⁺HSC/HPC 细胞中 SA-β-半乳糖阳性染色(p<0.05)。与 D-半乳糖模型组相比,Rg1 可显著增强 Sca-1⁺HSC/HPC 细胞中 CFU-Mix 的形成能力(p<0.05)。与 D-半乳糖模型组相比,Rg1 可显著降低 Sca-1⁺HSC/HPC 细胞的 G0/G1 期(p<0.05)。与 D-半乳糖模型组相比,Rg1 可显著降低裂解的 caspase-3 和 Bax 的表达,增加 Bcl-2 的表达(p<0.05)。与 D-半乳糖模型组相比,Rg1 治疗组可显著上调 SIRT3 和 SOD2 的表达(p<0.05)。

结论

Rg1 通过抑制线粒体途径介导的细胞凋亡和激活 SIRT3/SOD2 信号通路,在 D-半乳糖诱导的衰老模型中对 Sca-1⁺HSC/HPC 细胞发挥抗衰老作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1486/7163334/e595eaa7e46e/medscimonit-26-e920666-g001.jpg

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