D-硫酸多糖抗血管平滑肌细胞增殖作用及其机制

目的：探讨硫酸多糖（DPS）抗增殖作用及其机制，方法；用MTT法评价DPS抗大鼠主动脉平滑肌细胞（VSMC）增殖作用，用流式细胞仪观察DPS对VSMC胞浆内游离Ca^2 的含量、细胞周期和蛋白质含量的影响。结果：DPS在0.001-100mg/L浓度下，对AngⅡ诱导的VSMC增殖均有明显抑制作用，最佳抑制浓度为1mg/L，流式细胞术分析结果表明，DPS在抗增殖的浓度（1mg/L）下能抑制VSMC从G0/G1到S期的转换，阻止VSMC进入G2/M期；减少VSMC蛋白质的合成、DPS能明显抑制胞浆内游离Ca^2 浓度的升高，此作用可被一氧化氮合酶抑制剂（L-NAME）所阻断，提示一氧化氮可能介导了DPS降低胞浆内游离Ca^2 浓度的作用。结论：硫酸多糖DPS可拮抗AngⅡ诱导的VSMC增殖，其作用机理可能与降低胸浆内游离Ca^2 浓度，抑制VSMC的DNA及蛋白质合成有关。

Antiproliferative effects of D-polymannuronic sulfate on rat vascular smooth muscle cells and its related mechanisms

AIM: To investigate the inhibitory effects of D-polymannuronic sulfate (DPS) on the proliferation of rat vascular smooth muscle cells (VSMC) induced by angiotensin II (Ang II) and its related mechanisms. METHODS: The effects of DPS on Ang II-induced proliferation of VSMC were evaluated by MTT assay. The intracellular free Ca2+ concentrations, protein contents, and cell cycle were analyzed by flow cytometry. RESULTS: DPS 0.001 - 100 mg/L blocked the cell cycle at the G0/G1-->S transit and prevented the cells from entering into the G2/M phase, and its inhibitory effects on an increase in intracellular free Ca2+ concentrations and the protein synthesis of VSMC were also observed. Also, the suppressing actions of DPS on intracellular Ca2+ were completely blocked by L-NAME, a nitric oxide synthase inhibitor, indicating that the counteracting effects on a rise in intracellular free Ca2+ contents by DPS might be mediated by participation of NO. CONCLUSION: DPS exerted an inhibitory effect on Ang II-induced proliferation of VSMC and its related mechanisms were considered to be related to its inhibition on the increment of intracellular Ca2+ concentrations, which subsequently suppressed the synthesis of DNA and protein of VSMC.