GLOMERULAR PROSTAGLANDIN AND THROMBOXANE SYNTHESIS IN RAT NEPHROTOXIC SERUM NEPHRITIS - EFFECTS ON RENAL HEMODYNAMICS
GLOMERULAR PROSTAGLANDIN AND THROMBOXANE SYNTHESIS IN RAT NEPHROTOXIC SERUM NEPHRITIS - EFFECTS ON RENAL HEMODYNAMICS
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DOI：
10.1172/jci111100
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发表时间：
1983-01-01
影响因子：
15.9
通讯作者：
DUNN, MJ
中科院分区：
文献类型：
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作者：
LIANOS, EA;ANDRES, GA;DUNN, MJ
用放射免疫法测定抗肾小球基底膜（GBM）抗体诱导的肾小球肾炎大鼠离体肾小球花生四烯酸环氧化反应。在单次静脉内注射兔抗大鼠GBM血清后，早在2-3小时就观察到肾小球血栓烷B2（TxB 2）合成的增强，其中PGF 2 α的增量较小，PGE 2和6-酮-PGF 1 α。合成率。在疾病的第2天，肾小球合成TxB 2，并且在较小程度上合成PGF 2 α。和PGE 2仍然增强，而在第8，11和14天，TxB 2是唯一的前列腺素合成率增加。肾小球TxB 2的合成与presacrifice 24小时蛋白排泄。静脉内输注抗GMG血清后60分钟，肾小球滤过率（GFR）降低（0.66 ± 0.99）。0.04至0.44 . ±. 0.03 ml/min/100 g，P < 0.05），肾血浆流量（RPF）无显著变化：1.97 ± 0.05。0.23到1.80 .+-。0.23 ml/min/100 g），而肾小球PG合成速率无变化。在2小时时，GFR和RPF达到最低点（0.25 ± 0.25）。0.04和1.3 .+-。0.1 ml/min/100 g）与肾小球TxB 2增加5倍一致。到3小时，GFR和RPF部分恢复至0.43 ± 0.45。0.07和1.77 . ±. 0.20 ml/min/100 g，P < 0.05，尽管TxB 2合成进一步增加。GFR和RPF的恢复与血管舒张性PG（PGE 2和PGI 2）的增加一致。血栓素合成酶抑制剂OKY-1581（β- [4-（2-羧基-1-丙烯基）苄基]吡啶）在1、2和3 h显著抑制血小板和肾小球TxB 2的合成，并保护GFR。另一种血栓素合成酶抑制剂UK-38485也完全抑制血小板和肾小球TxB 2的合成，并阻止GFR在2和3 h的下降。环氧化酶抑制剂布洛芬可抑制血小板TxB 2和PGE 2的合成，并显著降低肾小球PGE 2的合成，但不影响TxB 2的合成。在布洛芬治疗的大鼠中，GFR和RPF在3 h的部分恢复减弱。体外肾小球TxB 2合成与牺牲前GFR和滤过分数呈负相关。在抗GBM肾炎中，肾小球中TxA 2和PG的合成增强，其介导肾血流动力学的变化。
Glomerular arachidonate cyclooxygenation by isolated rat glomeruli was assessed in vitro in antiglomerular basement membrane (anti-GBM) antibody-induced glomerulonephritis by radioimmunoassay for prostaglandins (PG) and thromboxane. After a single i.v. injection of rabbit anti-rat GBM serum, enhancement of glomerular thromboxane B2 (TxB2) synthesis was observed as early as 2-3 h with smaller increments in PGF2.alpha., PGE2 and 6-keto-PGF1.alpha. synthetic rates. On day 2 of the disease, the glomerular synthesis of TxB2 and, to a lesser extent, PGF2.alpha. and PGE2 remained enhanced, whereas on days 8, 11 and 14, TxB2 was the only prostanoid synthesized at increased rates. Glomerular TxB2 synthesis correlated with the presacrifice 24-h protein excretion. Sixty minutes after i.v. infusion of anti-GMG serum, glomerular filtration rate (GFR) decreased (0.66 .+-. 0.04 to 0.44 .+-. 0.03 ml/min per 100 g, P < 0.05), without a significant change in renal plasma flow (RPF): 1.97 .+-. 0.23 to 1.80 .+-. 0.23 ml/min per 100 g) and without a change in glomerular PG synthetic rates. At 2 h, GFR and RPF reached a nadir (0.25 .+-. 0.04 and 1.3 .+-. 0.1 ml/min per 100 g, respectively) coinciding with a 5-fold increment in glomerular TxB2. By 3 h the GFR and RPF partially recovered to 0.43 .+-. 0.07 and 1.77 .+-. 0.20 ml/min per 100 g, respectively, P < 0.05, despite further increments in TxB2 synthesis. This recovery of GFR and RPF coincided with increments in vasodilatory PG, (PGE2 and PGI2). The thromboxane synthetase inhibitor OKY-1581 (.beta.-[4-(2-carboxyl-1-propenyl)benzyl]pyridine) markedly inhibited platelet and glomerular TxB2 synthesis and preserved GFR at 1, 2 and 3 h. Another thromboxane synthetase inhibitor, UK-38485, also completely inhibited platelet and glomerular TxB2 synthesis and prevented decrements of GFR at 2 and 3 h. A cyclooxygenase inhibitor, ibuprofen, inhibited platelet TxB2 and PGE2 synthesis and significantly reduced glomerular PGE2 but not TxB2 synthesis. In the ibuprofen-treated rats, the partial recoveries of GFR and RPF at 3 h were attenuated. The in vitro glomerular TxB2 synthesis correlated inversely with the presacrifice GFR and filtration fraction. In anti- GBM nephritis there is enhanced synthesis of TxA2 and PG in the glomerulus that mediate changes in renal hemodynamics.