Molecular mechanisms of diabetic nephropathy and its therapeutic intervention.
Molecular mechanisms of diabetic nephropathy and its therapeutic intervention.
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DOI：
10.2174/138945007781386884
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发表时间：
2007-07
影响因子：
3.2
通讯作者：
S. Yamagishi;K. Fukami;S. Ueda;S. Okuda
中科院分区：
文献类型：
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作者：
S. Yamagishi;K. Fukami;S. Ueda;S. Okuda
糖尿病肾病是终末期肾功能衰竭的主要原因，这可能是糖尿病患者残疾和高死亡率的原因。糖尿病肾病的发生似乎是代谢和血流动力学因素相互作用的结果，这些因素激活了导致肾脏损害的常见途径。最近具有里程碑意义的大型临床研究表明，强化血糖控制可降低糖尿病肾病的发生和进展风险，阻断肾素-血管紧张素系统(RAS)也是糖尿病肾病代谢和血流动力学紊乱的重要靶点。然而，在发达国家，糖尿病肾病仍然是终末期肾功能衰竭的主要原因。因此，开发针对糖尿病肾病的新的治疗策略可能对大多数糖尿病患者有帮助。高糖通过增加氧化应激和晚期糖基化终产物(AGEs)的产生，激活RAS和蛋白激酶C(PKC)等多种机制，引发血管炎症，改变生长因子和细胞因子的基因表达，从而可能参与糖尿病肾病的发生发展。本文综述了糖尿病肾病的分子机制，以及即使在存在高血糖的情况下也可以预防这种破坏性疾病的潜在治疗干预措施，目前的治疗方案往往很难控制这种疾病。
Diabetic nephropathy is a leading cause of end-stage renal failure, which could account for disabilities and high mortality rates in patients with diabetes. Diabetic nephropathy seems to occur as a result of an interaction between metabolic and hemodynamic factors, which activate common pathways that lead to renal damage. Recent large landmark clinical studies have shown that intensive glucose control reduces the risk of the development and progression of diabetic nephropathy, and the blockade renin-angiotensin system (RAS) is also an important target for both metabolic and hemodynamic derangements in diabetic nephropathy. However, diabetic nephropathy remains the leading cause of end-stage renal failure in developed countries. Therefore, to develop novel therapeutic strategies that specifically target diabetic nephropathy may be helpful for most patients with diabetes. High glucose, via various mechanisms such as increased production of oxidative stress and advanced glycation end products (AGEs), and activation of the RAS and protein kinase C (PKC), elicits vascular inflammation and alters gene expression of growth factors and cytokines, thereby it might be involved in the development and progression of diabetic nephropathy. This article summarizes the molecular mechanisms of diabetic nephropathy and the potential therapeutic interventions that may prevent this devastating disorder even in the presence of hyperglycemia, control of which is often difficult with current therapeutic options.