Novel therapeutic targets for diabetic nephropathy
Novel therapeutic targets for diabetic nephropathy
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DOI：
10.2174/187153007780832118
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发表时间：
2007-06-01
影响因子：
1.9
通讯作者：
Okuda, S.
中科院分区：
文献类型：
--
作者：
Fukami, K.;Yamagishi, S.;Okuda, S.
糖尿病肾病是导致终末期肾功能衰竭的主要原因，这可能导致糖尿病患者的残疾和高死亡率。糖尿病肾病似乎是代谢和血液动力学因素相互作用的结果，这些因素激活了导致肾损伤的共同途径。近年来的大型前瞻性临床研究表明，强化血糖控制可有效降低糖尿病患者的微血管并发症，而肾素-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。高糖通过氧化应激和晚期糖基化终产物（AGEs）的产生增加、RAS和蛋白激酶C（PKC）的激活以及多元醇通路的刺激等多种机制，促进血管炎症反应，改变生长因子和细胞因子的基因表达，从而参与糖尿病肾病的发生和发展。因此，开发专门针对这些代谢和血流动力学紊乱的新的治疗策略是糖尿病肾病患者所期望的。在这篇综述中，我们讨论了糖尿病肾病的分子机制，并回顾了这一毁灭性疾病的有前途的治疗靶点。
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 prospective clinical studies have shown that intensive glucose control reduces microvascular complications effectively among patients with diabetes, and the renin-angiotensin system (RAS) is also an important target for both metabolic and hemodynamic derangements in diabetic nephropathy. High glucose,, via various mechanisms such as increased production of oxidative stress and advanced glycation end products (AGEs), activation of the RAS and protein kinase C (PKC), and stimulation of the polyol pathway, 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. Therefore, to develop novel therapeutic strategies that specifically target these metabolic and hemodynamic derangements is desired for patients with diabetic nephropathy. In this review, we discuss the molecular mechanisms of diabetic nephropathy and review the promising therapeutic targets for this devastating disorder.