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基质金属蛋白酶作为缺血/再灌注损伤的药物靶点。

Matrix metalloproteinases as drug targets in ischemia/reperfusion injury.

机构信息

Department for Molecular Biomedical Research, VIB, Ghent, Belgium.

出版信息

Drug Discov Today. 2011 Sep;16(17-18):762-78. doi: 10.1016/j.drudis.2011.06.009. Epub 2011 Jul 2.

Abstract

Deficient blood supply (ischemia) is a common consequence of some surgical procedures and certain pathologies. Once blood circulation is re-established (reperfusion), a complex series of events results in recruitment of inflammatory cells, rearrangement of the extracellular matrix and induction of cell death, which lead to organ dysfunction. Although ischemia/reperfusion (I/R) injury is an important cause of death, there is no effective therapy targeting the molecular mechanism of disease progression. Matrix metalloproteinases (MMPs), which are important regulators of many cellular activities, have a central role in disease progression after I/R injury, as suggested by numerous studies using MMP inhibitors or MMP-deficient mice. Here, we review the involvement of MMP activity in the various processes following I/R injury and the therapeutic potential of MMP inhibition.

摘要

血液供应不足(缺血)是某些外科手术和某些病理的常见后果。一旦血液循环得到恢复(再灌注),一系列复杂的事件会导致炎症细胞的募集、细胞外基质的重新排列和细胞死亡的诱导,从而导致器官功能障碍。尽管缺血/再灌注(I/R)损伤是死亡的一个重要原因,但针对疾病进展的分子机制还没有有效的治疗方法。基质金属蛋白酶(MMPs)是许多细胞活动的重要调节剂,许多使用 MMP 抑制剂或 MMP 缺陷小鼠的研究表明,它们在 I/R 损伤后的疾病进展中起着核心作用。在这里,我们回顾了 MMP 活性在 I/R 损伤后各种过程中的作用以及 MMP 抑制的治疗潜力。

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