Rincon-Choles Hernan, Kasinath Balakuntalam S, Gorin Yves, Abboud Hanna E
Division of Nephrology, Department of Medicine, The South Texas Veterans Health Care System (Audie L. Murphy Division) and The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900, USA.
Kidney Int Suppl. 2002 Dec(82):S8-11. doi: 10.1046/j.1523-1755.62.s82.3.x.
The renin-angiotensin system (RAS) and growth factors mediate structural and functional changes during the course of diabetic nephropathy (DN). Studies in humans and experimental models with DN suggest their involvement in the development and progression of DN. Activation of renal tissue RAS and increased expression of growth factors have been demonstrated at early stages of the disease. Angiotensin II and growth factors alter renal hemodynamics and exert trophic changes in renal cells that eventually result in fibrosis through direct mechanisms or through the release of other mediators. Their effects are likely modulated by metabolic changes including high glucose and free fatty acids. While blockade of the RAS ameliorates DN in humans, such evidence for blockade of growth factors is still lacking. It is likely that susceptibility to the development of DN and therapeutic efficacy are modulated by genetic polymorphisms in components of the RAS and growth factors including their receptors and other target molecules. Approaches to understand the intricate relationship between these systems and the mechanism(s) by which they alter capillary permeability and result in structural changes are areas of fruitful investigation.
肾素-血管紧张素系统（RAS）和生长因子在糖尿病肾病（DN）病程中介导结构和功能变化。在人类和DN实验模型中的研究表明它们参与了DN的发生和发展。在疾病早期已证实肾组织RAS激活和生长因子表达增加。血管紧张素II和生长因子改变肾血流动力学并在肾细胞中引起营养性变化，最终通过直接机制或通过释放其他介质导致纤维化。它们的作用可能受包括高血糖和游离脂肪酸在内的代谢变化调节。虽然阻断RAS可改善人类DN，但仍缺乏阻断生长因子的此类证据。DN发生的易感性和治疗效果可能受RAS和生长因子（包括其受体和其他靶分子）成分的基因多态性调节。了解这些系统之间复杂关系以及它们改变毛细血管通透性并导致结构变化的机制的方法是富有成效的研究领域。
