Ziyadeh F N
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, USA.
Miner Electrolyte Metab. 1995;21(4-5):292-302.
Renal injury in diabetes mellitus is a major cause of morbidity and mortality in diabetic patients. There is a clear correlation between the degree of glomerular as well as tubulointerstitial lesions and the development of reduced glomerular filtration rate. The important role of hyperglycemia in the genesis of diabetic renal disease has been strengthened by the application of tissue culture techniques. Recent in vitro studies, first in tubular epithelial cells and subsequently in the three glomerular cell types, have provided supportive evidence that high ambient glucose per se stimulates the synthesis of extracellular matrix components. Increased matrix synthesis and decreased degradation are thought to contribute to matrix accumulation in diabetic nephropathy. These processes are not mutually exclusive and they may be operating simultaneously but at different rates, with increased synthesis predominating early and decreased breakdown later in the course of the disease. Likely mediators of the effects of high glucose involve activation of the polyol pathway, altered myo-inositol metabolism, increased protein kinase C activity, and/or nonenzymatic glycation of various matrix proteins. A role for various growth factors, especially transforming growth factor-beta, also seems likely. However, the details of the cell-signaling mechanisms and the putative molecular mediators of the effect of hyperglycemia remain to be firmly established.
糖尿病肾病是糖尿病患者发病和死亡的主要原因。肾小球及肾小管间质病变程度与肾小球滤过率降低的发生之间存在明显的相关性。组织培养技术的应用进一步证实了高血糖在糖尿病肾病发生过程中的重要作用。最近的体外研究，先是在肾小管上皮细胞，随后在三种肾小球细胞类型中进行，提供了支持性证据，表明高糖本身会刺激细胞外基质成分的合成。基质合成增加和降解减少被认为是导致糖尿病肾病中基质积聚的原因。这些过程并非相互排斥，它们可能同时发生但速率不同，在疾病过程中，合成增加在早期占主导，而降解减少在后期占主导。高糖作用的可能介质包括多元醇途径的激活、肌醇代谢改变、蛋白激酶C活性增加和/或各种基质蛋白的非酶糖基化。各种生长因子，尤其是转化生长因子-β，似乎也发挥了作用。然而，细胞信号传导机制的细节以及高血糖作用的假定分子介质仍有待明确确定。
