Matsumori A, Ono K, Okada M, Miyamoto T, Sato Y, Sasayama S
Department of Cardiovascular Medicine, Kyoto University, 54 Kawaracho Shogoin, Sakyo-ku, Kyoto 606, Japan.
J Mol Cell Cardiol. 1998 Oct;30(10):2145-9. doi: 10.1006/jmcc.1998.0783.
Circulating levels of hepatocyte growth factor (HGF)/scatter factor have been recently found to be increased in the early phase of myocardial infarction, and it has been hypothesized that HGF plays a role in angiogenesis and collateral vessel growth. Heparin has also been shown to enhance angiogenesis and to improve collateral blood flow. This study was designed to study the effect of heparin on the release of HGF. In an experimental study, heparin was given to rats intravenously and plasma was collected for measurements of HGF by enzyme-linked immunosorbent assay. A dose-dependent increase in circulating HGF was measured with peak levels occurring 10 min after injection of 300 units/kg of heparin (15.4+/-2.0 ng/ml after v 0. 17+/-0.14 ng/ml before injection,P<0.0001). In a subsequent clinical study, 12 patients received 3000 units of heparin during cardiac catheterization. Circulating HGF increased steeply within 3 min of the injection. Comparable changes in plasma concentrations were measured in samples obtained from femoral vein (8.7+/-3.5 after v 0. 33+/-0.07 before injection P<0.05) or artery (10.5+/-3.2 ng/mlv 0. 27+/-0.05 P<0.01), pulmonary artery (9.1+/-2.0 ng/mlv 0.36+/-0.06 ng/ml,P=0.07 ) or right atrium (8.5+/-1.6 ng/mlv 0.42+/-0.11,P<0.01). This study suggests that heparin-induced effects such as the promotion of angiogenesis may be at least partly due to the release of HGF.
最近发现，心肌梗死早期循环中的肝细胞生长因子（HGF）/分散因子水平升高，并且据推测HGF在血管生成和侧支血管生长中发挥作用。肝素也已被证明可促进血管生成并改善侧支血流。本研究旨在探讨肝素对HGF释放的影响。在一项实验研究中，给大鼠静脉注射肝素，并收集血浆，通过酶联免疫吸附测定法测量HGF。检测到循环中的HGF呈剂量依赖性增加，在注射300单位/千克肝素后10分钟达到峰值水平（注射后为15.4±2.0纳克/毫升，而注射前为0.17±0.14纳克/毫升，P<0.0001）。在随后的一项临床研究中，12名患者在心脏导管插入术期间接受了3000单位的肝素。注射后3分钟内循环中的HGF急剧增加。在从股静脉（注射后为8.7±3.5，而注射前为0.33±0.07，P<0.05）、动脉（10.5±3.2纳克/毫升对0.27±0.05，P<0.01）、肺动脉（9.1±2.0纳克/毫升对0.36±0.06纳克/毫升，P=0.07）或右心房（8.5±1.6纳克/毫升对0.42±0.11，P<0.01）采集的样本中，检测到血浆浓度有类似变化。本研究表明，肝素诱导的诸如促进血管生成等效应可能至少部分归因于HGF的释放。
