Zoja C, Remuzzi G
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Pediatr Nephrol. 1995 Aug;9(4):495-502. doi: 10.1007/BF00866739.
There is increasing evidence that platelets are involved in the pathogenesis of glomerulonephritis. Intraglomerular platelets or their degradation products are observed in biopsies from patients with lupus nephritis, mesangioproliferative, membranous or IgA nephropathy. Moreover shortened platelet survival in patients with various glomerular diseases has also been described. In models of experimental glomerulonephritis, platelets may participate in glomerular injury, together with other mediators, by complex mechanisms. As extensively documented, platelets release within the glomerulus vasoactive, chemotactic and mitogenic substance that interact with a number of soluble mediators generated by renal resident or inflammatory cells and contribute to amplify glomerular injury. Thus platelet-activating factor and other platelet secretory products, polycationic macromolecules, platelet factor 4 and beta-thromboglobulin, alter glomerular permeability to proteins and enhance immune-mediated glomerular injury. Platelet-derived factors, like platelet-derived growth factor (PDGF) and transforming growth factor beta (TGF beta) mediate renal disease progression in experimental and human glomerulonephritis via their chemotactic activity for infiltrating leucocytes and their effect of promoting extracellular matrix synthesis by resident renal cells. In these settings increased renal expression of PDGF and TGF beta has correlated with clinical features. Specific PDGF and TGF beta inhibitors ameliorated experimental glomerular disease. A wide variety of therapies to inhibit platelet function have been employed over the years, however the results of clinical studies are controversial and do not allow conclusions to be drawn about the efficacy of anti-platelet agents in progressive renal disease. Identification of specific platelet inhibitors or interventions specific for platelet secretory products and their target cells will be crucial for understanding the exact role of platelets and their products in glomerular disease.
越来越多的证据表明血小板参与了肾小球肾炎的发病机制。在狼疮性肾炎、系膜增生性肾炎、膜性肾病或IgA肾病患者的活检组织中可观察到肾小球内的血小板或其降解产物。此外，也有报道称各种肾小球疾病患者的血小板生存期缩短。在实验性肾小球肾炎模型中，血小板可能通过复杂机制与其他介质一起参与肾小球损伤。正如大量文献记载的那样，血小板在肾小球内释放血管活性、趋化性和促有丝分裂物质，这些物质与肾脏固有细胞或炎症细胞产生的多种可溶性介质相互作用，从而加剧肾小球损伤。因此，血小板活化因子和其他血小板分泌产物、聚阳离子大分子、血小板因子4和β-血小板球蛋白会改变肾小球对蛋白质的通透性，并增强免疫介导的肾小球损伤。血小板衍生因子，如血小板衍生生长因子（PDGF）和转化生长因子β（TGFβ），通过其对浸润白细胞的趋化活性以及促进肾脏固有细胞合成细胞外基质的作用，在实验性和人类肾小球肾炎中介导肾脏疾病进展。在这些情况下，肾脏中PDGF和TGFβ表达的增加与临床特征相关。特异性PDGF和TGFβ抑制剂可改善实验性肾小球疾病。多年来已采用了多种抑制血小板功能的疗法，然而临床研究结果存在争议，无法就抗血小板药物在进行性肾脏疾病中的疗效得出结论。鉴定特异性血小板抑制剂或针对血小板分泌产物及其靶细胞的干预措施对于理解血小板及其产物在肾小球疾病中的确切作用至关重要。
