Benigni A, Remuzzi G
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Semin Nephrol. 1996 May;16(3):151-9.
Experimental and human studies indicate that altered glomerular permeability to proteins correlates with tubulointerstitial injury and subsequent glomerular scarring. Maneuvers that restore the selectivity of glomerular barrier to macromolecules limit renal injury in progressive nephropathies. The abnormal traffic of proteins through the glomerular capillary has an intrinsic renal toxicity linked to the process of over-reabsorption by proximal tubular cells. Excessive protein reabsorption induces functional alterations of tubular cells that overexpress inflammatory and vasoactive molecules, as indicated by in vitro or in vivo studies. Thus monocyte chemoattractant protein-1 and osteopontin may attract inflammatory cells into renal interstitium. Enhanced tubular endothelin-1 secretion, mainly toward the basolateral membrane of the cell, may stimulate interstitial macrophage infiltration and in addition may promote interstitial fibroblast proliferation and extracellular matrix synthesis, thus amplifying tubulointerstitial inflammation and injury.
实验研究和人体研究表明，肾小球对蛋白质通透性的改变与肾小管间质损伤及随后的肾小球瘢痕形成相关。恢复肾小球屏障对大分子物质选择性的措施可限制进行性肾病中的肾损伤。蛋白质通过肾小球毛细血管的异常转运具有与近端肾小管细胞过度重吸收过程相关的内在肾毒性。如体外或体内研究所表明的，过量的蛋白质重吸收会诱导肾小管细胞的功能改变，使其过度表达炎症和血管活性分子。因此，单核细胞趋化蛋白-1和骨桥蛋白可能会将炎症细胞吸引到肾间质。肾小管内皮素-1分泌增加，主要朝向细胞的基底外侧膜，可能刺激间质巨噬细胞浸润，此外还可能促进间质成纤维细胞增殖和细胞外基质合成，从而加剧肾小管间质炎症和损伤。
