Lelcuk S, Alexander F, Kobzik L, Valeri C R, Shepro D, Hechtman H B
Surgery. 1985 Aug;98(2):207-12.
Since prostacyclin (PGI2) is known to regulate renal cortical blood flow and since ischemia stimulates thromboxane (Tx) A2 synthesis, the role of these prostanoids in moderating the response to renal ischemia was studied in the rat. At baseline, plasma TxB2 concentration in untreated animals (n = 13) was 357 pg/ml. The left renal pedicle was clamped for 45 minutes after a right nephrectomy (n = 16), which led after 5 minutes of reperfusion to a rise in TxB2 to 2825 pg/ml (p less than 0.001), but there was no change in 6-keto-PGF1 alpha. After 24 hours creatinine levels rose from 0.4 to 3.0 mg/dl (p less than 0.001), and left renal weight rose from 94% to 117% (p less than 0.001) relative to the weight of the right kidney. In nephrectomized but nonischemic sham control rats (n = 7), creatinine level was 0.9 mg/dl and kidney weight 91% after 24 hours. Pretreatment with OKY 046 (n = 13) (2 mg/kg administered intravenously) blocked ischemia-induced TxB2 synthesis, while 6-keto-PGF1 alpha levels rose from 96 to 302 pg/ml (p less than 0.001). There was no increase in creatinine levels or kidney weight relative to the sham group. Pretreatment with ibuprofen (n = 10) (12 mg/kg) or OKY 046 and ibuprofen (n = 9) inhibited TxB2 and 6-keto-PGF1 alpha synthesis, but creatinine levels and renal weight rose (p less than 0.001). Renal histology in OKY 046-pretreated animals was equal to that in nephrectomized controls, while all other ischemic groups showed tubular necrosis. Results indicate that a high PGI2/TxA2 ratio protects against renal ischemia.
由于已知前列环素（PGI2）可调节肾皮质血流，且缺血会刺激血栓素（Tx）A2的合成，因此在大鼠中研究了这些前列腺素在调节对肾缺血反应中的作用。在基线时，未处理动物（n = 13）的血浆TxB2浓度为357 pg/ml。在右侧肾切除术后（n = 16），将左侧肾蒂夹闭45分钟，再灌注5分钟后，TxB2升高至2825 pg/ml（p < 0.001），但6-酮-PGF1α无变化。24小时后，肌酐水平从0.4 mg/dl升至3.0 mg/dl（p < 0.001），相对于右侧肾脏重量，左侧肾脏重量从94%升至117%（p < 0.001）。在肾切除但未缺血的假手术对照大鼠（n = 7）中，24小时后肌酐水平为0.9 mg/dl，肾脏重量为91%。用OKY 046（n = 13）（静脉注射2 mg/kg）预处理可阻断缺血诱导的TxB2合成，而6-酮-PGF1α水平从96 pg/ml升至302 pg/ml（p < 0.001）。相对于假手术组，肌酐水平和肾脏重量没有增加。用布洛芬（n = 10）（12 mg/kg）或OKY 046与布洛芬（n = 9）预处理可抑制TxB2和6-酮-PGF1α的合成，但肌酐水平和肾脏重量仍升高（p < 0.001）。用OKY 046预处理的动物的肾脏组织学与肾切除对照动物相同，而所有其他缺血组均显示肾小管坏死。结果表明，高PGI2/TxA2比值可预防肾缺血。
