Fernando A R, Armstrong D M, Griffiths J R, Hendry W F, O'Donoghue E P, Perrett D, Ward J P, Wickham J E
Lancet. 1976 Mar 13;1(7959):555-7. doi: 10.1016/s0140-6736(76)90356-1.
The function of rat kidneys subjected to 60 minutes of warm ischaemia at body-temperature was notably protected by the prior administration of the purine nucleoside inosine as a 40 mg/ml solution maintained at 37 degrees C. With direct intrarenal arterial perfusion of the kidney at the onset of ischaemia or with intraperitoneal (i.p.) injection 40 minutes before ischaemia, the plasma-creatinine at 24 hours was significantly lower (P less than 0-001) than that of untreated 60-minute-ischaemia controls and not significantly different from that of non-ischaemic unilateral-nephrectomy controls. Intravenous inosine 20 minutes beforehand also afforded significant (P less than 0-01) protection. 7-day survival was 100% in 30 inosine-pretreated rats and 65% in 45 rats with all other types of pre-treatment (P less than 0-001). Although i.p. adenosine was better (P less than 0-05) than no treatment, i.p. inosine was better (P less than 0-02) than i.p. adenosine. Allopurinol, phenoxybenzamine, A.T.P., or cyclic A.M.P. caused no improvement over controls. Kidneys perfused with inosine maintained higher purine-nucleotide levels during ischaemia and rapidly resynthesised A.T.P. when blood-flow was restored in vivo.
将嘌呤核苷肌苷以40mg/ml的溶液形式维持在37℃预先给药，可显著保护大鼠肾脏在体温下经历60分钟热缺血后的功能。在缺血开始时直接对肾脏进行肾内动脉灌注，或在缺血前40分钟进行腹腔注射，24小时时的血浆肌酐水平显著低于未治疗的60分钟缺血对照组（P<0.001），且与非缺血单侧肾切除对照组无显著差异。提前20分钟静脉注射肌苷也能提供显著（P<0.01）的保护作用。30只经肌苷预处理的大鼠7天存活率为100%，45只采用所有其他预处理方式的大鼠7天存活率为65%（P<0.001）。尽管腹腔注射腺苷比不治疗要好（P<0.05），但腹腔注射肌苷比腹腔注射腺苷更好（P<0.02）。别嘌呤醇、酚苄明、三磷酸腺苷（ATP）或环磷酸腺苷（cAMP）并未比对照组有改善。用肌苷灌注的肾脏在缺血期间维持较高的嘌呤核苷酸水平，并在体内恢复血流时迅速重新合成ATP。
