The role of specific Nox isoforms in diabetic renal disease and atherosclerosis

糖尿病在全球和澳大利亚都在增加。大多数糖尿病患者最终会发展为肾病，并死于心脏病发作和中风等血管并发症。氧化应激（产生与体内其他蛋白质快速反应的氧自由基，导致组织损伤）已被认为在糖尿病患者中观察到的肾脏和血管疾病中起重要作用。这项提案将试图识别和测量肾脏和血管中参与氧化应激产生的特定蛋白质。我们的目标是确定这些蛋白质中哪一个是最重要的。我们将详细评估这些蛋白质是如何工作的，以及哪些其他因素被激活导致组织损伤。这些研究的最终目标是找到新的治疗方案，以减少肾脏和血管壁中有害分子的产生，从而减少糖尿病中的肾衰竭、心脏病发作、中风和坏疽。在我们的研究中，我们将使用已经用于糖尿病患者的药物来治疗高血压。在初步研究中，我们已经证明这些药物也可以降低氧化应激。此外，我们将使用新的，更具体的治疗有害的蛋白质。通过与来自德国的Harald施密特教授及其团队的合作，他们最近搬到了墨尔本的莫纳什大学，我们将有机会获得有害蛋白质的特定基因被敲除的小鼠。当这些小鼠患糖尿病时，很可能会发生较少或没有肾脏和血管损伤。我们的研究将有助于确定与肾脏和血管疾病相关的最重要的氧化应激产生蛋白。这些知识将为糖尿病患者提供更有效和更有效的治疗方法，以预防，停止甚至改善肾脏和血管疾病，从而减少这一高危患者群体的残疾和死亡。

Diabetes is increasing worldwide and in Australia. The majority of patients with diabetes eventually will develop kidney disease and will die of blood vessel complications such as heart attacks and stroke. Oxidative stress (the generation of free oxygen radicals that react quickly with other proteins in the body causing tissue damage) has been suggested to play an important role in kidney and blood vessel disease observed in diabetic patients. This proposal will try to identify and measure specific proteins in the kidney and vessels that are involved in the production of oxidative stress. We aim to define which one of these proteins is the most important. We will assess in detail how these proteins work and which other factors are activated leading to tissue damage. The ultimate goal of these studies is to find new treatment options to decrease the production of harmful molecules in the kidney and blood vessel wall thereby reducing kidney failure, heart attacks, stroke and gangrene in diabetes. In our studies, we will use medications already used in patients to treat high blood pressure in diabetes. In preliminary studies we have shown that these drugs also reduce oxidative stress. Furthermore, we will use novel, more specific treatments that the harmful ptoteins. Through a collaboration with Professor Harald Schmidt and his group from Germany who have recently moved to Monash University in Melbourne we will have access to mice in which specific genes for harmful proteins have been knocked out. These mice when made diabetic will most likely develop less or no kidney and blood vessel damage. Our studies will help to identify the most important oxidative stress producing protein associated with kidney and vessel disease. This knowledge will lead to more effective and more potent treatments for patients with diabetes to prevent, stop or even improve kidney and blood vessel disease thereby reducing disability and death in this high risk group of patients.