Docherty Neil G, O'Sullivan Orfhlaith E, Healy Declan A, Fitzpatrick John M, Watson R William G
Department of Surgery, Conway Institute of Biomolecular and Biomedical Sciences, Univ. College Dublin, Belfield, Dublin 4, Republic of Ireland.
Am J Physiol Renal Physiol. 2006 Jan;290(1):F4-13. doi: 10.1152/ajprenal.00045.2005.
Ureteric obstruction is frequently encountered in primary care urology and can lead to damage to the ipsilateral kidney. Relief of all types of obstruction generally leads to the normalization of any deterioration in renal function noted at diagnosis. However, some evidence from animal models suggests that obstruction can cause progressive deleterious effects on renal function and blood pressure control, especially in the presence of preexisting pathologies such as essential hypertension. The last 10 years have seen a proliferation of studies in rodents wherein complete unilateral ureteric obstruction has been used as a model of renal fibrosis. However, the relevance of the findings to human obstructive uropathy has, in many cases, not been the primary aim. In this review, we outline the major events linking damage to the renal parenchyma and cell death to the evolution of fibrosis following obstruction. Special focus is given to the role of apoptosis as a major cause of cell death during and post-complete ureteric obstruction. Several interventions that reduce tubular apoptosis are discussed in terms of their ability to prevent subsequent progression to end-organ damage and fibrosis.
输尿管梗阻在基层泌尿外科中经常遇到，可导致同侧肾脏受损。解除所有类型的梗阻通常会使诊断时发现的肾功能恶化恢复正常。然而，一些动物模型的证据表明，梗阻可对肾功能和血压控制产生渐进性有害影响，尤其是在存在原发性高血压等既往疾病的情况下。在过去10年中，啮齿动物研究激增，其中完全性单侧输尿管梗阻被用作肾纤维化模型。然而，在许多情况下，这些研究结果与人类梗阻性肾病的相关性并非主要目的。在本综述中，我们概述了梗阻后将肾实质损伤和细胞死亡与纤维化演变联系起来的主要事件。特别关注凋亡在完全性输尿管梗阻期间和之后作为细胞死亡主要原因的作用。讨论了几种减少肾小管凋亡的干预措施，这些措施具有预防随后进展为终末器官损伤和纤维化的能力。
