Näsström Birgit, Stegmayr Bernd, Olivecrona Gunilla, Olivecrona Thomas
Department of Public Health and Clinical Medicine, Nephrology, Umeå University, Sweden.
BMC Nephrol. 2004 Nov 3;5:17. doi: 10.1186/1471-2369-5-17.
Lipoprotein lipase (LPL) has a central role in the catabolism of triglyceride-rich lipoproteins. The enzyme is anchored to the vascular endothelium through interaction with heparan sulphate proteoglycans and is displaced from this interaction by heparin. When heparin is infused, there is a peak of LPL activity accompanied by a reduction in triglycerides (TG) during the first hour, followed by a decrease in LPL activity to a stable plateau during the remaining session while TG increase towards and beyond baseline. This suggests that tissue stores of LPL become depleted. It has been argued that low molecular weight (LMW) heparins cause less disturbance of the LPL system than conventional heparin does.
We have followed LPL activity and TG during a dialysis-session with a LMW heparin (dalteparin) using the same patients and regime as in a previous study with conventional heparin, i.e. a primed infusion.
The shape of the curve for LPL activity resembled that during the earlier dialyses with conventional heparin, but the values were lower during dialysis with dalteparin. The area under the curve for LPL activity during the peak period (0-180 minutes) was only 27% and for the plateau period (180-240 minutes) it was only 36% of that observed with conventional heparin (p < 0.01). These remarkably low plasma LPL activities prompted us to re-analyze LPL activity and to measure LPL mass in frozen samples from our earlier studies. There was excellent correlation between the new and old values which rules out the possibility of assay variations as a confounding factor. TG increased from 2.14 mmol/L before, to 2.59 mmol/L after the dialysis (p < 0.01). From 30 minutes on, the TG values were significantly higher after dalteparin compared to conventional heparin (p < 0.05).
These results indicate that LMW heparins disturb the LPL system as much or more than conventional heparin does.
脂蛋白脂肪酶(LPL)在富含甘油三酯的脂蛋白分解代谢中起核心作用。该酶通过与硫酸乙酰肝素蛋白聚糖相互作用而锚定在血管内皮上,并被肝素从这种相互作用中置换出来。输注肝素时,在第一个小时内会出现LPL活性峰值,同时甘油三酯(TG)水平降低,随后在剩余时间段内LPL活性下降至稳定平台期,而TG水平则朝着基线水平升高并超过基线。这表明LPL的组织储备被耗尽。有人认为,低分子量(LMW)肝素对LPL系统的干扰比传统肝素小。
我们采用与先前使用传统肝素的研究相同的患者和方案,即在预充式输注的情况下,在使用低分子量肝素(达肝素)进行透析的过程中监测LPL活性和TG水平。
LPL活性曲线的形状与先前使用传统肝素进行透析时相似,但在使用达肝素透析期间其值较低。在高峰期(0 - 180分钟)LPL活性曲线下面积仅为使用传统肝素时观察值的27%,在平台期(180 - 240分钟)仅为36%(p < 0.01)。这些显著较低的血浆LPL活性促使我们重新分析LPL活性,并测量我们早期研究中冷冻样本中的LPL质量。新旧值之间具有良好的相关性,排除了检测变异作为混杂因素的可能性。TG水平从透析前的2.14 mmol/L升高至透析后的2.59 mmol/L(p < 0.01)。从30分钟起,使用达肝素后的TG值明显高于使用传统肝素后的TG值(p < 0.05)。
这些结果表明,低分子量肝素对LPL系统的干扰与传统肝素相当或更大。