Abstract：
Chronic venous disease (CVD) is a proqgressive and underestimated condition related to a vicious circle established by venous reflux and endothelial inflammation, leading to vein dilation and histology distortion, including loss of media tone. Sulodexide (SDX) is a drug restoring the glycocalyx that demonstrated endothelial protection and permeability regulation, together with anti-thrombotic and anti-inflammatory roles. In the lab it also exhibited vein contractility function. The aim of the present study was to show the possible role of endothelium and nitric oxide pathway on SDX\'s veno-contractile effect on human saphenous veins. The remnants of great saphenous vein (GSV) segments (n = 14) were harvested during coronary artery bypass graft surgery. They were dissected as endothelium-intact (n = 8) and denuded rings (n = 6). First, a viability test was carried out in bath with Krebs-Henseleit solution to investigate a control and basal tension value. After this, cumulative doses of SDX were applied to rings and contraction values were studied in endothelium-intact phenylephrine (PheE, 6 × 10-7 M) pre-contracted vein rings. Finally, endothelium-intact PheE pre-contacted vein rings were treated by nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, 10-4 M) for 10 min. Contraction protocol was applied, and contraction values were measured in cumulative doses of SDX. The same protocol was applied to endothelium-denuded vein rings to investigate the effect of SDX. Saphenous vein rings showed an increase in contraction to cumulative doses of SDX. In endothel-intact rings, KCL-induced contraction from 92.6% ± 0.3 to 112.9% ± 0.4 with cumulative SDX doses. However, SDX did not show any veno-contractile effect on endothel-denuded rings. In denuded rings contraction responses measured from 94.9% ± 0.3 to 85.2% ± 0.3 with increasing doses of SDX, indicating no significant change. Nitric oxide synthase inhibitor (L-NAME) prohibited the contraction response of the sulodexide in all dosages, indicating that the contractile function of SDX was mediated by endothelial derived nitric oxide. Results of endothel-intact and denuded rings with L-NAME showed a similar incline with denuded rings with SDX only. The results confirmed SDX\'s veno-contractile effect in human samples, by means of nitric oxide synthase pathways involvement.
摘要：
慢性静脉疾病（CVD）是一种与静脉反流和内皮炎症建立的恶性循环有关的严重和低估的疾病，导致静脉扩张和组织学扭曲，包括媒体音调的损失。Sulodexide（SDX）是一种恢复糖萼的药物，表现出内皮保护和通透性调节，以及抗血栓和抗炎作用。在实验室中，它还表现出静脉收缩功能。本研究的目的是显示内皮和一氧化氮途径在SDX对人隐静脉的静脉收缩作用中的可能作用。在冠状动脉旁路移植术中收集大隐静脉（GSV）段的残余物（n=14）。将它们解剖为完整的内皮（n=8）和裸露的环（n=6）。首先,在Krebs-Henseleit溶液浴中进行生存力测试，以研究对照和基础张力值。在这之后,将SDX的累积剂量应用于环，并在内皮完整的去氧肾上腺素中研究了收缩值（PheE，6×10-7M）预收缩静脉环。最后,用一氧化氮合酶抑制剂Nω-硝基-L-精氨酸甲酯（L-NAME，10-4M）持续10分钟。应用了收缩协议，以SDX的累积剂量测量收缩值。将相同的方案应用于内皮剥脱的静脉环以研究SDX的作用。大隐静脉环对累积剂量的SDX显示收缩增加。在内部完整的环中，在累积SDX剂量下,KCL诱导的收缩从92.6%±0.3至112.9%±0.4。然而,SDX对内皮剥脱的环没有任何静脉收缩作用。随着SDX剂量的增加，在从94.9％±0.3到85.2％±0.3的裸露环收缩反应中，表明没有显著变化。一氧化氮合酶抑制剂（L-NAME）在所有剂量下都能抑制舒洛地特的收缩反应，表明SDX的收缩功能是由内皮源性一氧化氮介导的。L-NAME完整和裸露的环的结果显示，仅SDX的裸露环具有相似的倾斜度。结果证实了SDX在人体样本中的静脉收缩效应，通过一氧化氮合酶途径参与。
