Araki H, Lefer A M
Prostaglandins Med. 1979 Apr;2(4):277-84. doi: 10.1016/0161-4630(79)90061-2.
Since prostaglandin E1 (PGE1) is known to have a beneficial effect in hemorrhagic shock, a biologically active derivative of PGE1, 6-keto-PGE1, was examined for its effect on traumatic shock in rats. In sham-operated rats, infusion of 6-keto-PGE1, at a rate of 250 ng/kg/min intravenously decreased arterial blood pressure by 23 mm Hg at 5 hr. In rats subjected to Noble-Collip drum trauma, infusion of 6-keto-PGE1, starting 15 min after the trauma, significantly improved the survival time from 1.0 +/- 0.1 to 2.6 +/- 0.3 hr compared to rats given only the vehicle (i.e., Tris buffer). The improved survival was accompanied by a diminished plasma accumulation of the cardiotoxic peptide, myocardial depressant factor (MDF), and the lysosomal protease cathepsin D. 6-keto-PGE1 also exerted a direct lysosomal stabilizing effect in isolated cat liver lysosomes, as well as reducing cardiac afterload in rats. It is concluded that 6-keto-PGE1 protects in traumatic shock by hemodynamic as well as cytoprotective actions.
由于已知前列腺素E1(PGE1)在失血性休克中具有有益作用,因此研究了PGE1的一种生物活性衍生物6-酮-PGE1对大鼠创伤性休克的影响。在假手术大鼠中,以250 ng/kg/min的速率静脉输注6-酮-PGE1,5小时时动脉血压降低23 mmHg。在遭受Noble-Collip鼓撞击创伤的大鼠中,创伤后15分钟开始输注6-酮-PGE1,与仅给予赋形剂(即Tris缓冲液)的大鼠相比,存活时间从1.0±0.1小时显著延长至2.6±0.3小时。存活时间的延长伴随着心脏毒性肽、心肌抑制因子(MDF)和溶酶体蛋白酶组织蛋白酶D的血浆蓄积减少。6-酮-PGE1在离体猫肝溶酶体中也具有直接的溶酶体稳定作用,并且还降低了大鼠的心脏后负荷。得出的结论是,6-酮-PGE1通过血流动力学和细胞保护作用对创伤性休克起到保护作用。