Enhanced glomerular prostaglandin formation in experimental membranous nephropathy.
Enhanced glomerular prostaglandin formation in experimental membranous nephropathy.
复制标题
实验性膜性肾病中肾小球前列腺素形成增强。
DOI：
10.1038/ki.1987.118
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发表时间：
1987
影响因子：
19.6
通讯作者：
Couser,WG
中科院分区：
文献类型：
--
作者：
Stahl,RA;Adler,S;Baker,PJ;Chen,YP;Pritzl,PM;Couser,WG
实验性膜性肾病肾小球前列腺素形成增强。为了确定免疫介导的肾小球损伤是否影响肾小球细胞环氧化酶产物的形成，我们测定了被动型Heymann肾炎（PHN）大鼠离体肾小球中前列腺素E_2（PGE_2）和血栓素B_2（TXA_2的稳定代谢产物）的形成。PHN是由抗体和补体介导的膜性肾病模型，不依赖于炎性细胞。通过注射大鼠近端肾小管刷状缘抗原（Fx 1A）的异源抗体诱导PHN后5天，大鼠出现蛋白尿36.5 ± 34（对照组3.8 ± 1 mg/天）。用眼镜蛇毒因子治疗，使补体C3水平降低至基线的10%以下，可预防蛋白尿的发生（6.9 ± 2 mg/天）。上皮下、肾小球免疫复合物沉积和蛋白尿的发展与肾小球PGE 2（87%）和TXB 2（183%）形成的显著刺激相关。在用眼镜蛇毒因子消耗补体的动物中，肾小球前列腺素类生物合成的这种增加被显著抑制（PGE 2增加22%，TXB 2增加75%）。眼镜蛇毒因子对正常大鼠肾小球前列腺素样物质的形成无影响。在另外的实验中，我们验证了TXA 2可能有助于PHN蛋白尿的介导的假设。我们使用了血栓素合成酶抑制剂UK 38485。UK 38485使PHN大鼠肾小球TXB_2生成减少80%，但不影响125 I标记抗体在肾小球的沉积，也不改变PHN大鼠的尿蛋白排泄量（对照组42 ± 21，UK 38485，39 ± 24 mg/d，P > 0.05）。我们的数据表明，PHN大鼠肾小球损伤与体内肾小球细胞产生的TXB 2和PGE 2增加有关。这种肾小球免疫沉积物形成对前列腺素类合成的刺激作用被全身性补体耗竭所抑制。我们的数据不支持TXB 2在该动物模型中介导蛋白尿的致病作用。
Enhanced glomerular prostaglandin formation in experimental membranous nephropathy. To determine whether the induction of immune–mediated glomerular injury influences the formation of cyclooxy-genase products by glomerular cells, we determined prostaglandin E2(PGE2) and thromboxane B2(TXB2) (as the stable metabolite of TXA2) formation in isolated glomeruli of rats with passive Heymann nephritis (PHN). PHN is a model of membranous nephropathy mediated by antibody and complement independent of inflammatory cells. Five days following induction of PHN by injection of heterologous antibody to rat proximal tubular brush border antigen (Fx1A) rats developed proteinuria 36.5 ± 34 (controls 3.8 ± 1 mg/day). Treatment with cobra venom factor, which depleted complement C3 levels to less than 10% of baseline, prevented the development of proteinuria (6.9 ± 2 mg/day). The development of subepithelial, glomerular immune–complex deposits and proteinuria was associated with a significant stimulation of glomerular PGE2(87%) and TXB2(183%) formation. This increment in glomerular prostanoid biosynthesis was significantly inhibited (PGE2increased 22%, TXB2increased 75%) in animals that were complement depleted with cobra venom factor. Cobra venom factor had no effect on glomerular prostanoid formation in normal rats. In additional experiments we tested the hypothesis that TXA2may contribute to mediation of proteinuria in PHN. We utilized a thromboxane synthetase inhibitor UK38485. UK38485 reduced glomercular TXB2formation by 80% without influencing glomerular deposition of125I-labeled antibody, and did not alter levels of urine protein excretion in rats with PHN (control 42 ± 21, UK 38485, 39 ± 24 mg/day, P > 0.05). Our data demonstrate that glomerular injury in rats with PHN is associated with increased TXB2and PGE2production which derives from glomerular cells in vivo. This stimulatory effect of glomerular immune–deposit formation on prostanoid synthesis is inhibited by generalized systemic complement depletion. Our data do not support a pathogenic role for TXB2in the mediation of proteinuria in this animal model.