中文摘要：

探讨5-氟尿嘧啶（5-fluorouracil,5-FU）对人骨髓基质细胞（human bone marrow stromal cell,h BMSC）的损伤作用机制;当归多糖（angelica sinensis polysaccharides,ASP）对5-氟尿嘧啶损伤h BMSC的保护作用。采用CCK-8法测定人骨髓基质细胞株HS-5对不同浓度5-FU（0μg/m L,12.5μg/m L,25μg/m L,50μg/m L和100μg/m L）的敏感性。流式细胞术分析细胞周期;β-半乳糖苷酶染色检测衰老细胞;DCFH-DA荧光染色流式检测胞内活性氧（reactive oxygen species,ROS）水平;酶学法检测谷胱甘肽过氧化物酶（glutathione peroxidase,GSH-Px）、超氧化物歧化酶（superoxide dismutase,SOD）含量;流式细胞术分析γH2AX表达水平;ELISA检测8-羟基脱氧鸟苷（8-hydroxydeoxyguanosine,8-OHd G）的含量;5-FU 12.5~100μg/m L抑制HS-5增殖,抑制作用具有浓度依赖性和时间依赖性。5-FU组较与对照组相比细胞周期发生G1期阻滞,β-半乳糖苷酶染色阳性率升高;胞内ROS含量显著升高;细胞抗氧化能力降低;γH2AX和8-OHd G表达水平增高。ASP治疗组较5-FU组细胞相比细胞周期阻滞减少;衰老细胞比率降低;胞内ROS含量显著降低;细胞抗氧化能力升高;DNA损伤指标表达水平降低。5-FU可通过增强氧化应激诱发DNA损伤致骨髓基质细胞衰老;ASP对骨髓基质细胞损伤有保护作用,其机制可能与ASP降低损伤后骨髓基质细胞氧化应激减轻DNA损伤从而延缓骨髓基质细胞衰老有关。

英文摘要：

To investigate the mechanism of injured human bone marrow stromal cells induced by 5-fluo- rouraciland protective effect of Angelica Polysaccharide on impaired hBMSC induced by 5-fluorouracil. The Cell Counting Kit-8 for determining the sensitivity of HS-5 cells which were derived from human bone marrow stroreal cell line to the different doses of 5-fluorouracil （0 μg/mL, 12.5 μg/mL, 25 μg/mL, 50 μg/mL and 100 μg/mL） in vitro was utilized. 5-Fluorouracil from 12.5-100 μg/mL inhibited the proliferation of HS-5 cells in a dose-dependent and time-dependent manner. Compared with the control group, the cell cycle of 5-FU group was blocked in G1 phase and the ratio of senescent HS-5 cells increased. The intracellular ROS content significantly increased and the antioxidant capacity also attenuated. The Expression of γH2AX and 8-OHdG significantly increased. Com pared with the 5-FU group, the cell cycle arrest decreased in the ASP treatment group and the ratio of senescent HS-5 cells decreased; the intracellular ROS content significantly decreased and the antioxidant capacity also boosted up; the expression level of DNA damage index also decreased. 5-fluorouracil can led to the senescence of bone marrow stromal cell through boosting oxidation stress which induces the DNA damage. The mechanism of angelica polysaccharides having protective effect on the damage of bone marrow stromal cell may be relevant to the decrease DNA damage of angelica polysaccharides on oxidation stress of bone marrow stromal cell, and preventing the senescence of bone marrow stromal cells.