Leehey D J, Uckerman M T, Rahman M A
Department of Medicine, Hines Veterans Administration Hospital, IL 60141.
J Lab Clin Med. 1989 Mar;113(3):309-15.
Although there is considerable evidence that vasodilator prostaglandins such as prostaglandin E2 (PGE2) modulate renal hemodynamics in liver cirrhosis, the role of the vasoconstrictor thromboxane A2 (TXA2) is controversial. We measured renal hemodynamics and glomerular eicosanoid production in cirrhotic and control rats. Renal plasma flow, as estimated by para-aminohippurate clearance (CPAH) and glomerular filtration rate, as determined by inulin clearance (CIN), were comparable between groups; glomerular production of PGE2 and TXA2 (estimated by the metabolite thromboxane B2 [TXB2]) was slightly but not significantly higher in cirrhotic than in control rats (PGE2: 1060 +/- 142 pg/mg glomerular protein vs 854 +/- 288 pg/mg glomerular protein; TXB2: 782 +/- 103 pg/mg glomerular protein vs 468 +/- 104 pg/mg glomerular protein). Addition of serum from cirrhotic rats to the incubation media failed to increase eicosanoid production in glomeruli obtained from either cirrhotic or control rats. Cyclooxygenase inhibition with 5 mg/kg indomethacin, a dose sufficient to result in a 68% inhibition of glomerular PGE2 synthesis, decreased both CPAH (from 6.59 +/- 0.69 ml/min to 4.52 +/- 0.67 ml/min, p less than 0.05) and CIN (from 1.34 +/- 0.16 ml/min to 0.68 +/- 0.07 ml/min, p less than 0.01) in cirrhotic rats. Thromboxane synthesis inhibition with 1 mg/kg UK-38485, which resulted in an 84% decrease in glomerular TXB2, did not significantly affect either CPAH or CIN; however, there was a strong trend toward improvement in CIN (from 1.23 +/- 0.11 ml/min to 1.43 +/- 0.15 ml/min (0.05 less than p less than 0.1). Neither drug affected renal hemodynamics in control rats.(ABSTRACT TRUNCATED AT 250 WORDS)
尽管有大量证据表明，诸如前列腺素E2（PGE2）等血管舒张性前列腺素可调节肝硬化患者的肾血流动力学，但血管收缩性血栓素A2（TXA2）的作用仍存在争议。我们测定了肝硬化大鼠和对照大鼠的肾血流动力学及肾小球类花生酸生成情况。通过对氨基马尿酸清除率（CPAH）估算的肾血浆流量以及通过菊粉清除率（CIN）测定的肾小球滤过率在两组之间相当；肝硬化大鼠肾小球中PGE2和TXA2（通过代谢产物血栓素B2 [TXB2]估算）的生成量略高于对照大鼠，但差异无统计学意义（PGE2：1060±142 pg/mg肾小球蛋白对854±288 pg/mg肾小球蛋白；TXB2：782±103 pg/mg肾小球蛋白对468±104 pg/mg肾小球蛋白）。将肝硬化大鼠的血清添加至孵育培养基中，未能增加来自肝硬化大鼠或对照大鼠的肾小球类花生酸生成量。用5 mg/kg消炎痛抑制环氧化酶，该剂量足以使肾小球PGE2合成受到68%的抑制，可使肝硬化大鼠的CPAH（从6.59±0.69 ml/min降至4.52±0.67 ml/min，p<0.05）和CIN（从1.34±0.16 ml/min降至0.68±0.07 ml/min，p<0.01）均降低。用1 mg/kg UK-38485抑制血栓素合成，可使肾小球TXB2降低84%，对CPAH或CIN均无显著影响；然而，CIN有明显改善趋势（从1.23±0.11 ml/min升至1.43±0.15 ml/min（0.05<p<0.1）。两种药物均未影响对照大鼠的肾血流动力学。（摘要截取自250字）
