Bianchini P, Liverani L, Mascellani G, Parma B
Opocrin S.p.A. Research Laboratories, Corlo (Modena), Italy.
Semin Thromb Hemost. 1997;23(1):3-10. doi: 10.1055/s-2007-996063.
The heterogeneity of unfractionated heparins (Hep) can be correlated to the species and organs of origin and to the process of production. Heparins, extracted by different, validated processes from different organs and/or tissues (mucosa, thymus, pancreas, placenta, lung, intestine) or mammals (pig, beef, sheep, man) and other vertebrates (chicken), have been examined by HPLC analysis of heparinase digests. By analysis of disaccharides many observations have been made. Porcine mucosa heparin (pm-Hep) was always found to contain higher amounts of the disaccharides delta UA-GlcNS,6S and delta UA-2S-GlcNS,6S, than did bovine mucosa heparin (bm-Hep), whereas bm-Hep always showed higher amounts of the sequence IdoA(2OSO3)-GlcNSO3 than did pm-Hep. These findings mean that the last step of the biosynthesis, the 6-O-sulfation of glucosamine-N-sulfate (GlcNSO3), is accomplished; in bm-Hep, to a lesser extent than in pm-Hep. The 6-O-sulfated molar fractions of pig mucosa, chicken intestine, beef pancreas, beef placenta, and beef lung heparins were higher than the corresponding molar fractions of beef mucosa and beef thymus Heps. Also the manufacturing processes can partially rearrange the heparin structure. Even 6-O-sulfation enrichment (by chromatographic purification) or base-catalyzed displacement of sulfate groups from IdoA2SO3 occurred. The resulting anticoagulant activity roughly correlated with the percentage of trisulfated disaccharide and the 6-O-sulfated molar fraction. The heparin from human placenta was similar to pm-Hep. The observed species- and organ-dependent structural characteristics support the suggestion by Nader and Dietrich (in Heparin, Chemical and Biological Properties, Lane DA, U Lindahl (Eds). Arnold, London, 1989, p 81) on the antipathogenic role of heparin. The 6-O-sulfation of glucosamine, present in higher amounts in organs that function as barriers against many foreign bodies, like lung, placenta, intestine of chicken and pig, may play an important role in this antipathogenic action of Hep.
普通肝素（Hep）的异质性与来源的物种和器官以及生产过程相关。通过不同的、经过验证的方法从不同器官和/或组织（黏膜、胸腺、胰腺、胎盘、肺、肠）或哺乳动物（猪、牛、羊、人）以及其他脊椎动物（鸡）中提取的肝素，已通过肝素酶消化产物的高效液相色谱分析进行了检测。通过对二糖的分析，得出了许多观察结果。猪黏膜肝素（pm - Hep）总是比牛黏膜肝素（bm - Hep）含有更高量的二糖δUA - GlcNS,6S和δUA - 2S - GlcNS,6S，而bm - Hep总是比pm - Hep显示出更高量的IdoA(2OSO3)-GlcNSO3序列。这些发现意味着生物合成的最后一步，即氨基葡萄糖 - N - 硫酸盐（GlcNSO3）的6 - O - 硫酸化已经完成；在bm - Hep中，程度低于pm - Hep。猪黏膜、鸡肠、牛胰腺、牛胎盘和牛肺肝素的6 - O - 硫酸化摩尔分数高于牛黏膜和牛胸腺肝素的相应摩尔分数。制造过程也可以部分地重新排列肝素结构。甚至发生了6 - O - 硫酸化富集（通过色谱纯化）或IdoA2SO3中硫酸根的碱催化取代。由此产生的抗凝活性大致与三硫酸化二糖的百分比和
