Pescador R, Tettamanti R, Salvetti L, Conto A, Barone D, Porta R, Mantovani M, Ferro L
Crinos Biological Research Laboratories, Villa Guardia (Como), Italy.
Life Sci. 1995;57(6):579-89. doi: 10.1016/0024-3205(95)00308-s.
The antithrombotic drug Defibrotide (DFT) (a polydeoxyribonucleotide with a mean MW of 20,000 Daltons) reduces the number of leukocytes and platelets in thrombi. Because leukocytes and platelets are of importance in the genesis of endothelial lesions leading to atherosclerosis, DFT was given to challenge leukocytosis in rabbits with diet-induced atherosclerosis (0.25% cholesterol for 16 weeks). After 9 weeks of cholesterol feeding and at the end of experiment, oral DFT (60 mg/Kg per day) had decreased the leukocyte count raised by the cholesterol diet. Leukocyte stickiness and leukocyte differential counts were not modified by either oral cholesterol or by oral cholesterol plus oral DFT. At the end of experiment, oral DFT had normalized the platelet count increased by cholesterol diet. The red blood cell count decreased by oral cholesterol at 9 weeks and at the end of experiment was normalized by DFT. The % of aortae endothelial surface involved in the atherosclerotic process was decreased by oral DFT. The frequencies of intimal thickening in blood vessels of kidneys and hearts and in cardiac valves were reduced by oral DFT by 47%, 29% and 17%, although these reductions were not statistically significant. It is suggested that DFT, by preventing the increase in the number of leukocytes and platelets and deactivating them, as demonstrated in papers already published, was able to counteract against the atherosclerotic process.
抗血栓药物去纤苷（DFT）（一种平均分子量为20,000道尔顿的多聚脱氧核糖核苷酸）可减少血栓中的白细胞和血小板数量。由于白细胞和血小板在导致动脉粥样硬化的内皮损伤发生过程中具有重要作用，因此给予DFT来挑战饮食诱导的动脉粥样硬化兔子（16周给予0.25%胆固醇）中的白细胞增多症。在给予胆固醇9周后以及实验结束时，口服DFT（每天60毫克/千克）降低了由胆固醇饮食引起的白细胞计数。口服胆固醇或口服胆固醇加口服DFT均未改变白细胞黏附性和白细胞分类计数。在实验结束时，口服DFT使由胆固醇饮食增加的血小板计数恢复正常。红细胞计数在9周时因口服胆固醇而降低，在实验结束时由DFT使其恢复正常。口服DFT降低了参与动脉粥样硬化过程的主动脉内皮表面百分比。口服DFT使肾脏和心脏血管以及心脏瓣膜内膜增厚的频率分别降低了47%、29%和17%，尽管这些降低在统计学上不显著。有人提出，如已发表的论文中所证明的，DFT通过防止白细胞和血小板数量增加并使其失活，能够对抗动脉粥样硬化过程。
