Semenov A V, Mazurov A V, Preobrazhenskaia M E, Ushakova N A, Mikhaĭlov V I, Berman A E, Usov A I, Nifant'ev N E, Bovin N V
Institute of Experimental Cardiology, Cardiology Research Center, Moscow.
Vopr Med Khim. 1998 Mar-Apr;44(2):135-44.
The inhibitory effects of sulfated polysaccharides-fucoidan and heparin on P-selectin-ligand interaction in vitro and on the ability of fucoidan to inhibit the leukocyte extravasation in rat peritonitis were studied. The lectin activity of P-selectin in vitro was based on its ability to bind lectin-labeled synthetic ligand, Sialyl-Lea/x, conjugated with polyacrylamide (PAA). Fucoidan and heparin inhibited binding of labeled ligand to both purified P-selectin and the activated platelets expressing P-selectin on their surface. The inhibitory effect of fucoidan 100-fold higher than that of heparin. As P-selectin plays an important role at an earlier stage of the inflammation process, the antiinflammatory action of fucoidan on P-selectin-dependent peritonitis in rats was studied. Peritonitis was induced by intraperitoneal injection of the peptone solution and was characterized by an increase in total cell number and neutrophil percentage in rat peritone exudate. Intravenous injection of fucoidan was found to cause a dose- and time-dependent reduction of neutrophil extravasation into inflamed peritoneum. The minimal dose of fucoidan, that was able to produce 96.8 +/- 2.9% inhibition of neutrophil extravasation--if administered within the first 15 min after peptone-B was 0.8 mg per rat. Significant effect of fucoidan injection (about 80% inhibition) was also obtained 1.5 h after the induction of inflammation. Fucoidan administered 2.5 h after peptone had virtually no effect on neutrophil extravasation. The data obtained show that fucoidan blocks the inflammation process at its earlier stages--most probably at the expense of its interaction with P-selectin.
研究了硫酸化多糖岩藻依聚糖和肝素在体外对P-选择素-配体相互作用的抑制作用，以及岩藻依聚糖抑制大鼠腹膜炎中白细胞渗出的能力。P-选择素在体外的凝集素活性基于其与结合了凝集素标记的合成配体唾液酸化路易斯寡糖（Sialyl-Lea/x）并与聚丙烯酰胺（PAA）偶联的能力。岩藻依聚糖和肝素抑制标记配体与纯化的P-选择素以及表面表达P-选择素的活化血小板的结合。岩藻依聚糖的抑制作用比肝素高100倍。由于P-选择素在炎症过程的早期阶段起重要作用，因此研究了岩藻依聚糖对大鼠P-选择素依赖性腹膜炎的抗炎作用。通过腹腔注射蛋白胨溶液诱导腹膜炎，其特征是大鼠腹腔渗出液中总细胞数和中性粒细胞百分比增加。发现静脉注射岩藻依聚糖会导致中性粒细胞向炎症腹膜的渗出呈剂量和时间依赖性减少。如果在注射蛋白胨B后的前15分钟内给药，能够产生96.8±2.9%中性粒细胞渗出抑制作用的岩藻依聚糖的最小剂量为每只大鼠0.8毫克。在炎症诱导后1.5小时注射岩藻依聚糖也获得了显著效果（约80%的抑制）。在注射蛋白胨2.5小时后给予岩藻依聚糖对中性粒细胞渗出几乎没有影响。获得的数据表明，岩藻依聚糖在炎症的早期阶段阻断炎症过程，很可能是以其与P-选择素的相互作用为代价。
