目的 研究海洋硫酸多糖(DPS)对大鼠血管平滑肌细胞(VSMC)增殖的影响及其作用机制。方法 建立碱性成纤维细胞生长因子(bFGF)和白介素-1(IL-1)所诱导的VSMC增殖模型,以MTT法观察DPS对VSMC增殖的影响，分别用Griess重氮化反应法和放免法测定VSMC上清液中一氧化氮(NO)、血管紧张素II(Ang II)和内皮素-1(ET-1)的含量。结果 DPS在0.01-10 μg*mL-1浓度下，对bFGF或IL-1所致的VSMC增殖均有明显抑制作用。DPS呈剂量依赖性增加NO合成及降低Ang II和ET-1的生成或释放。结论 DPS对VSMC增殖有抑制作用，其机制可能与增加一氧化氮合成及降低血管紧张素II和内皮素-1的生成或释放有关。%AIM To investigate the inhibitory effects of D-polymannuronic sulfate (DPS) on the proliferation of rat vascular smooth muscle cells (VSMC) induced by basic fibroblast growth factor (bFGF) or interleukin-1 (IL-1) and its related mechanisms. METHODS Rat aortic smooth muscle cells pretreated with DPS in concentrations ranging from 0.001 μg*mL-1 up to 100 μg*mL-1 were incubated at 37℃ for 24 h, followed by addition of bFGF (50 ng*mL-1) or IL-1 (50 U*mL-1) for another 24 h. The effects of DPS on the proliferation of VSMC were evaluated by MTT assays. VSMC were pretreated with DPS in concentrations ranging from 0.001 μg*mL-1 up to 1 μg*mL-1, followed by addition of L-NAME (0.1 μg*mL-1) or bFGF (50 ng*mL-1) for 24 h. Supernatant nitric oxide (NO) was determined with NO assay kit, while supernatant angiotensin II (Ang II) and endothelin-1 (ET-1) were measured by radioimmunoassay. RESULTS DPS exerted antiproliferative effects at concentrations ranging from 0.01 μg*mL-1 to 10 μg*mL-1, and its maximal effect was observed at the concentration of 1 μg*mL-1. Also, the suppressing actions of DPS on the proliferation of VSMC were diminished by increasing the concentrations of bFGF or IL-1. Furthermore, DPS increased NO synthesis and decreased Ang II and ET-1 contents released from VSMC in a concentration-dependent manner. CONCLUSION DPS afforded the antiproliferative effects on bFGF- or IL-1-treated VSMC and its underlying mechanisms were associated with enhancement of NO synthesis and decrement of Ang II and ET-1 production/release in vitro.
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