Sharma K, Ziyadeh F N
Department of Medicine, Thomas Jefferson University, Philadelphia, PA, USA.
Semin Nephrol. 1997 Mar;17(2):80-92.
The important role of hyperglycemia in the genesis of diabetic renal disease has been strengthened by tissue culture studies, experimental animal models, and clinical trials. A mechanistic understanding of the cellular and biochemical processes that link hyperglycemia with the development of diabetic nephropathy is indispensable for directing the most optimal therapeutic interventions. Likely mediators of the effects of high ambient glucose include activation of the polyol pathway, increased protein kinase C activity, nonenzymatic glycation of circulating or matrix proteins, and/or aberrant synthesis or actions of cytokines and vasomodulatory agents. The latter include angiotensin II, thromboxane, platelet-derived growth factor, endothelins, insulin-like growth factor-1, and transforming growth factor-beta. The studies we review here argue strongly in support of the hypothesis that elevated production and/or activity of transforming growth factor-beta in the kidney is a final common mediator of diabetic renal hypertrophy and mesangial matrix expansion.
组织培养研究、实验动物模型和临床试验均强化了高血糖在糖尿病肾病发生过程中的重要作用。对于将高血糖与糖尿病肾病发展联系起来的细胞和生化过程的机制性理解，对于指导最优化的治疗干预不可或缺。高环境葡萄糖效应的可能介质包括多元醇途径的激活、蛋白激酶C活性增加、循环蛋白或基质蛋白的非酶糖基化，和/或细胞因子及血管调节因子的异常合成或作用。后者包括血管紧张素II、血栓素、血小板衍生生长因子、内皮素、胰岛素样生长因子-1和转化生长因子-β。我们在此回顾的研究有力地支持了这样一种假说，即肾脏中转化生长因子-β产生增加和/或活性增强是糖尿病性肾肥大和系膜基质扩张的最终共同介质。
