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先兆子痫及其他妊娠高血压综合征患者肾小球中几种基底膜蛋白的蓄积。肾前列腺素和纤连蛋白的可能作用。

Accumulation of several basement membrane proteins in glomeruli of patients with preeclampsia and other hypertensive syndromes of pregnancy. Possible role of renal prostaglandins and fibronectin.

作者信息

Foidart J M, Nochy D, Nusgens B, Foidart J B, Mahieu P R, Lapiere C M, Lambotte R, Bariety J

出版信息

Lab Invest. 1983 Sep;49(3):250-9.

PMID:6887782
Abstract

The glomerular lesions of preeclampsia consist of swelling of endothelial cells, interposition of mesangial cells and matrix between the endothelial cells and the glomerular basement membrane, and organization of subendothelial deposits of incompletely characterized material. Fibrin and immunoglobulins have previously been localized to these deposits. Laminin, a large basement membrane glycoprotein, type IV collagen, fibronectin, and a basement membrane proteoglycan were found in moderate amounts in the mesangium and prominently in the thickened glomerular capillary walls of patients with preeclampsia or other hypertensive syndromes of pregnancy. Fibrin showed the same pattern of distribution as that of fibronectin. The material deposited in the subendothelial layer of the capillary loops thus consists not only of plasma-derived proteins but also structural components of the glomerular basement membrane and of the mesangial matrix. Type I collagen deposits were demonstrated only in mesangium of pregnant patients with chronic or recurrent hypertension. Glomerular epithelial and mesangial cells synthesize in vitro the basement membrane proteins that accumulate in glomeruli of pregnant hypertensive patients. We have tested the influence of some of the pathophysiologic changes occurring during preeclampsia on the biosynthesis of collagen by rat glomerular epithelial and mesangial cells. Addition of indomethacin to the cultures transiently inhibited the synthesis of prostaglandins (PGE2) and of collagen. Addition of exogenous fibronectin to the media stimulated the production of collagen by mesangial and epithelial cells. Alterations in the metabolism of prostaglandins and the increased deposition of fibronectin observed during preeclampsia could thus play a pathogenic role in the accumulation of basement membrane proteins in glomeruli of these patients.

摘要

子痫前期的肾小球病变包括内皮细胞肿胀、系膜细胞及基质插入内皮细胞与肾小球基底膜之间,以及特征不完全明确的物质在内皮下沉积的机化。纤维蛋白和免疫球蛋白先前已定位到这些沉积物中。层粘连蛋白是一种大型基底膜糖蛋白,IV型胶原、纤连蛋白和一种基底膜蛋白聚糖在子痫前期或其他妊娠高血压综合征患者的系膜中含量中等,在增厚的肾小球毛细血管壁中含量显著。纤维蛋白的分布模式与纤连蛋白相同。因此,沉积在毛细血管袢内皮下层的物质不仅包括血浆来源的蛋白质,还包括肾小球基底膜和系膜基质的结构成分。I型胶原沉积物仅在患有慢性或复发性高血压的妊娠患者的系膜中被证实。肾小球上皮细胞和系膜细胞在体外合成在妊娠高血压患者肾小球中积累的基底膜蛋白。我们测试了子痫前期期间发生的一些病理生理变化对大鼠肾小球上皮细胞和系膜细胞胶原蛋白生物合成的影响。在培养物中添加吲哚美辛可暂时抑制前列腺素(PGE2)和胶原蛋白的合成。向培养基中添加外源性纤连蛋白可刺激系膜细胞和上皮细胞产生胶原蛋白。因此,子痫前期期间观察到的前列腺素代谢改变和纤连蛋白沉积增加可能在这些患者肾小球基底膜蛋白的积累中起致病作用。

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