Chaudhari A, Kirschenbaum M A
Biochim Biophys Acta. 1984 Feb 9;792(2):135-40. doi: 10.1016/0005-2760(84)90214-5.
The present studies were designed (1) to examine the pattern of changes in eicosanoid biosynthesis in isolated rat glomeruli, and (2) to correlate these changes with the previously observed alterations in renal perfusion and glomerular filtration rate which occur after uranyl nitrate administration, a model of toxin-induced acute renal failure. In the first part of this study, the in vitro and the in vivo effects of two cyclooxygenase inhibitors were examined for their ability to inhibit rat glomerular eicosanoid biosynthesis. Inhibition of prostaglandin E2 and prostaglandin F2 alpha generation by 1 mM aspirin in vitro was 76 and 82%, respectively. Similar inhibitions of 85 and 72% of biosynthesis of the above-mentioned lipids by 0.1 mM indomethacin were also noted. Intraperitoneal administration of aspirin (150 mg/kg) resulted in a significant inhibition of 88% or greater of prostaglandin E2, prostaglandin F2 alpha, 6-keto-prostaglandin F2 alpha, and thromboxane B2 biosynthesis. These results indicated that the expected alterations produced under in vivo conditions were detectable by in vitro techniques used in this study. 24 h after the administration of uranyl nitrate (25 mg/kg), significant increases in the biosynthesis of prostaglandin E2 (124%) and prostaglandin F2 alpha (88%) were observed when compared to the control values. No significant changes in prostacyclin or thromboxane formation were noted at this time. A further increase in the biosynthesis of prostaglandin E2 (248%), prostaglandin F2 alpha (262%), and a significant increase in prostacyclin (120%), measured as 6-keto-prostaglandin F1 alpha, were noted at 48 h. No changes in thromboxane B2 biosynthesis were noted. It is concluded that these data are consistent with the hypothesis that the increased glomerular biosynthesis of vasodilator eicosanoids (i.e., prostaglandin E2 and prostacyclin) may play a significant role in the homeostatic regulation of renal perfusion and glomerular filtration after acute toxic injury to the kidney.
（1）检测大鼠离体肾小球中类花生酸生物合成的变化模式；（2）将这些变化与硝酸铀酰给药后（一种毒素诱导的急性肾衰竭模型）先前观察到的肾灌注和肾小球滤过率的改变相关联。在本研究的第一部分，检测了两种环氧化酶抑制剂的体外和体内作用，以考察它们抑制大鼠肾小球类花生酸生物合成的能力。1 mM阿司匹林在体外对前列腺素E2和前列腺素F2α生成的抑制率分别为76%和82%。0.1 mM吲哚美辛对上述脂质生物合成的抑制率分别为85%和72%，也有类似的抑制效果。腹腔注射阿司匹林（150 mg/kg）导致前列腺素E2、前列腺素F2α、6-酮-前列腺素F2α和血栓素B2生物合成受到显著抑制，抑制率达88%或更高。这些结果表明，本研究中使用的体外技术可检测到体内条件下产生的预期变化。与对照值相比，在给予硝酸铀酰（25 mg/kg）24小时后，观察到前列腺素E2（124%）和前列腺素F2α（88%）的生物合成显著增加。此时，前列环素或血栓素的生成未见显著变化。在48小时时，前列腺素E2（248%）、前列腺素F2α（262%）的生物合成进一步增加，以6-酮-前列腺素F1α衡量的前列环素显著增加（120%）。血栓素B2生物合成未见变化。得出的结论是，这些数据与以下假设一致：血管舒张性类花生酸（即前列腺素E2和前列环素）肾小球生物合成增加可能在肾脏急性毒性损伤后肾灌注和肾小球滤过的稳态调节中起重要作用。
