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目的:考察肝素结构中影响抗人系膜细胞增殖活性的因素,如不同位点的硫酸基团,羧基、肝素的主链结构以及相对分子质量大小。方法:采用化学修饰的方法,分别制备2,3-O-脱硫酸化,6-O-脱硫酸化肝素,N-脱硫酸化肝素、高碘酸钠氧化-硼氢化钠还原肝素、多硫酸化肝素。APTT比较肝素衍生物的抗凝活性,MTT法比较这些肝素衍生物对血清引起人肾小球系膜细胞增殖的抑制作用。结果和结论:2,3-O-硫酸基团相对于6-O-硫酸基团、N-硫酸基团来说对抗血清引起的人肾小球系膜细胞增殖活性影响更大,硫酸基团的含量以及羧基影响抗增殖活性,但不是决定性的因素。肝素抗增殖活性同样不依赖于肝素主链结构的完整性、抗凝活性;当肝素相对分子质量大于4.5kD时,其抗增殖活性同样不依赖于其相对分子质量大小。
OBJECTIVE: To investigate the factors influencing the proliferation activity of anti-human mesangial cells in heparin structure, such as the main chain structure of sulfate group, carboxyl group and heparin in different sites and the relative molecular mass. Methods: 2,3-O-desulfated, 6-O-desulfated heparin, N-desulfated heparin, sodium periodate oxidized-sodium borohydride reduced heparin and polysulfated heparin were prepared by chemical modification. APTT compared anticoagulant activity of heparin derivatives, MTT assay of these heparin derivatives on serum-induced inhibition of human mesangial cell proliferation. RESULTS AND CONCLUSION: The 2,3-O-sulfate group has a greater effect on the proliferation activity of human mesangial cells induced by antiserum than the 6-O-sulfate group and the N-sulfate group. The sulfate group The content of carboxyl groups and anti-proliferative activity, but not a decisive factor. The antiproliferative activity of heparin also does not depend on the integrity and anticoagulant activity of the heparin backbone structure. When the relative molecular mass of heparin is more than 4.5 kD, its antiproliferative activity also does not depend on its relative molecular mass.