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具有高抗血栓、抗血脂和抗凝活性的两个肝素家族的分级分离及结构特征

Fractionation and structural features of two heparin families with high antithrombotic, antilipemic and anticoagulant activities.

作者信息

Bianchini P, Osima B, Parma B, Nader H B, Dietrich C P, Casu B, Torri G

出版信息

Arzneimittelforschung. 1985;35(8):1215-9.

PMID:4074437
Abstract

15 heparin preparations from bovine intestine, pancreas and lung and hog intestine were fractionated in two main components by selective barium precipitation. The ones that precipitated at room temperature with barium (slow moving (SM)-heparins) had a high anticoagulant activity measured by the USP and APTT (activated partial thromboplastin time) assay and low antithrombotic activity by the Yin and Wessler method. The fractions precipitated at 5 degrees C with barium (fast moving (FM)-heparins) had a low anticoagulant action and high antithrombotic activity. The maximum anti-Xa activity (chromogenic method) was present in heparins with molecular weights around 12-15 X 10(3) daltons whereas high APTT and LPL releasing activities were present in SM-heparins with molecular weights of 30-40 X 10(3) and 15-25 X 10(3) daltons, respectively. FM-heparins had a higher anti-Xa activity and lower lipoprotein lipase (LPL)-releasing activity when compared with the SM-heparins with the same molecular weights. Significant structural differences were observed between SM- and FM-heparins by 13C-NMR spectra and enzymatic degradation with heparinase and heparitinase from Flavobacterium heparinum. Also, significant differences were observed for anti-Xa and anticoagulant activities for the two types of heparins depending on the pharmacological assay used.

摘要

采用选择性钡沉淀法,对来自牛肠、胰腺、肺以及猪肠的15种肝素制剂进行分离,得到两个主要组分。室温下用钡沉淀的组分(慢泳(SM)-肝素),通过美国药典(USP)和活化部分凝血活酶时间(APTT)测定法测得其具有高抗凝活性,而用殷和韦斯勒方法测得其抗血栓活性较低。5℃下用钡沉淀的组分(快泳(FM)-肝素),具有低抗凝作用和高抗血栓活性。抗Xa活性最大值(发色底物法)存在于分子量约为12 - 15×10³道尔顿的肝素中,而高APTT和脂蛋白脂肪酶(LPL)释放活性分别存在于分子量为30 - 40×10³和15 - 25×10³道尔顿的SM-肝素中。与相同分子量的SM-肝素相比,FM-肝素具有更高的抗Xa活性和更低的脂蛋白脂肪酶(LPL)释放活性。通过¹³C-NMR光谱以及用来自肝素黄杆菌的肝素酶和类肝素酶进行酶解,观察到SM-肝素和FM-肝素之间存在显著的结构差异。此外,根据所使用的药理测定方法,两种类型的肝素在抗Xa和抗凝活性方面也观察到显著差异。

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Biochem J. 1997 Mar 1;322 ( Pt 2)(Pt 2):499-506. doi: 10.1042/bj3220499.
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[Low molecular weight heparin: how does it modify lipid metabolism in chronic hemodialysis patients?].
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