Kernoff P B, Willis A L, Stone K J, Davies J A, McNicol G P
Br Med J. 1977 Dec 3;2(6100):1441-4. doi: 10.1136/bmj.2.6100.1441.
The effects of orally ingested dihomo-gamma-linolenic acid (DHLA), the natural biosynthetic precursor of prostaglandin E1 (PGE1), were assessed in human volunteers. Single doses of DHLA (0.1--2g) increased the proportion of DHLA relative to arachidonic acid in plasma and platelets and also increased the ex-vivo capacity of platelets to produce PGE1 and PGE2. More pronounced effects were observed during sustained treatment (five days to four weeks) when DHLA also accumulated in red cell membranes. These biochemical changes were accompanied by potentially antithrombotic changes in haemostatic function. The most common effect, which was consistently detected after 0.1-g single doses of DHLA or its methyl ester, was a decrease in plasma heparin-neutralising activity. Inhibition of platelet aggregation induced by adenosine diphosphate was also detected, though this was generally less pronounced. Sustained treatment in one subject also produced definite inhibition of ristocetin-induced platelet aggregation. There was only one possible adverse effect--a transient cough in a subject with a history of asthma. DHLA therefore seems to have considerable potential as an agent for preventing and treating human thromboembolic disease.
在人类志愿者中评估了口服摄入的二高 - γ - 亚麻酸（DHLA）（前列腺素E1（PGE1）的天然生物合成前体）的效果。单剂量的DHLA（0.1 - 2克）增加了血浆和血小板中DHLA相对于花生四烯酸的比例，还提高了血小板体外产生PGE1和PGE2的能力。在持续治疗期间（五天至四周）观察到更明显的效果，此时DHLA也在红细胞膜中蓄积。这些生化变化伴随着止血功能方面潜在的抗血栓形成变化。最常见的效果是在单剂量0.1克的DHLA或其甲酯后始终检测到血浆肝素中和活性降低。还检测到对二磷酸腺苷诱导的血小板聚集的抑制作用，不过通常不太明显。对一名受试者的持续治疗也产生了对瑞斯托菌素诱导的血小板聚集的明确抑制作用。只有一个可能的不良反应——一名有哮喘病史的受试者出现短暂咳嗽。因此，DHLA作为预防和治疗人类血栓栓塞性疾病的药物似乎具有相当大的潜力。
