CD39 protects against renal ischaemic-reperfusion injury

在许多医疗环境中，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，并产生了一些有毒的变化。重新建立器官的血液流动对于防止进一步的损害是必不可少的，然而血液流动的重建本身可能对器官有害。血流、氧气和能量的回流实际上可以促进更广泛的损伤——这一过程被称为缺血再灌注损伤（IRI）。加深对IRI的了解应该有助于开发将其影响降至最低的药物。这项工作的总体目的是研究分子CD39在IRI中的作用。这种分子的理想位置是最大限度地减少伤害——它位于血管细胞上，因此，能够直接中和因这种伤害而释放的毒素。因此，我们认为，在这种情况下，它将具有保护作用。我们已经开发了表达这种分子的动物，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（包括心脏移植手术）中受到保护；与IRI共享许多特性的进程。此外，缺乏这种分子的小鼠容易发生更严重的IRI。我们的目标是通过使用缺乏和表达CD39的动物来研究这一点。肾脏的血流将中断30分钟并在24小时和48小时内评估肾功能。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。

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.