CD39 protects against renal ischaemic-reperfusion injury

CD39 预防肾缺血再灌注损伤

• 批准号: nhmrc : 447706
• 负责人: Prof Anthony D'Apice
• 金额: $ 29.44万
• 依托单位: The University of Melbourne
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/cd39-protects-renal-reperfusion-injury/76944
• 关键词: CD39; protects; against; renal; ischaemic

In many medical settings, such as heart attacks, strokes, transplantation, heart surgery, shock and infection, the blood supply to an organ may be compromised resulting in damage. The cessation of blood flow depletes the organ of oxygen and generates a number of toxic changes. Re-establishing blood flow to the organ is essential to prevent further damage, however the reestablishment of blood flow itself can be harmful to the organ. The return of blood flow, oxygen and energy can actually promote more widespread injury - a process known as ischaemia-reperfusion injury (IRI). A greater understanding of IRI should aid in the development of drugs that minimise its impact. The overall aim of this work is to examine the role of a molecule - CD39 - in IRI. This molecule is ideally situated to minimise injury - it is located on cells that line blood vessels and, as such, is able to directly neutralise toxins released in response to this injury. We, therefore, believe that it will be protective in this setting. We have developed animals that express this molecule and have preliminary results to suggest that these animals are protected in experimental models of IRI as well as in several other models including heart transplantation surgery; processes that share many features with IRI. Moreover, mice deplete of this molecule are prone to more severe IRI. We aim to investigate this by using animals both lacking and expressing CD39. Blood flow to the kidneys will be interrupted for 30 minutes and kidney function assessed at 24 and 48 hours. We will then delve into the potential mechanisms underpinning IRI by determining whether the kidney itself or the blood cells afford protection, which has direct clinical implications.

在许多医疗环境中，例如心脏病发作、中风、移植、心脏手术、休克和感染，器官的血液供应可能受到损害，导致损伤。血液流动的停止耗尽了器官的氧气，并产生了许多有毒的变化。重建流向器官的血流对于防止进一步损伤至关重要，然而，重建血流本身可能对器官有害。血流、氧气和能量的恢复实际上会促进更广泛的损伤--这一过程被称为缺血再灌注损伤（IRI）。对IRI的更深入了解应该有助于开发最大限度地减少其影响的药物。这项工作的总体目标是研究分子-CD 39-在IRI中的作用。这种分子的理想位置是最大限度地减少损伤-它位于血管内衬的细胞上，因此能够直接中和响应这种损伤而释放的毒素。因此，我们认为，在这种情况下，它将起到保护作用。我们已经开发出表达这种分子的动物，并有初步结果表明，这些动物在IRI的实验模型以及其他几种模型中受到保护，包括心脏移植手术;与IRI共享许多特征的过程。此外，缺乏这种分子的小鼠容易发生更严重的IRI。我们的目的是通过使用缺乏和表达CD 39的动物来研究这一点。将中断流向肾脏的血流30分钟，并在24和48小时评估肾功能。然后，我们将通过确定肾脏本身或血细胞是否提供保护来深入研究IRI的潜在机制，这具有直接的临床意义。