Mullins Linda J, Conway Bryan R, Menzies Robert I, Denby Laura, Mullins John J
University of Edinburgh/British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
University of Edinburgh/British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
Dis Model Mech. 2016 Dec 1;9(12):1419-1433. doi: 10.1242/dmm.027276.
The rat has classically been the species of choice for pharmacological studies and disease modeling, providing a source of high-quality physiological data on cardiovascular and renal pathophysiology over many decades. Recent developments in genome engineering now allow us to capitalize on the wealth of knowledge acquired over the last century. Here, we review rat models of hypertension, diabetic nephropathy, and acute and chronic kidney disease. These models have made important contributions to our understanding of renal diseases and have revealed key genes, such as Ace and P2rx7, involved in renal pathogenic processes. By targeting these genes of interest, researchers are gaining a better understanding of the etiology of renal pathologies, with the promised potential of slowing disease progression or even reversing the damage caused. Some, but not all, of these target genes have proved to be of clinical relevance. However, it is now possible to generate more sophisticated and appropriate disease models in the rat, which can recapitulate key aspects of human renal pathology. These advances will ultimately be used to identify new treatments and therapeutic targets of much greater clinical relevance.
长期以来,大鼠一直是药理学研究和疾病建模的首选物种,在过去几十年里,它为心血管和肾脏病理生理学提供了高质量的生理数据来源。基因组工程的最新进展使我们能够利用上世纪积累的丰富知识。在此,我们综述高血压、糖尿病肾病以及急慢性肾病的大鼠模型。这些模型为我们理解肾脏疾病做出了重要贡献,并揭示了参与肾脏致病过程的关键基因,如Ace和P2rx7。通过靶向这些感兴趣的基因,研究人员对肾脏病理的病因有了更深入的了解,有望减缓疾病进展甚至逆转所造成的损害。其中一些(但并非全部)靶基因已被证明具有临床相关性。然而,现在有可能在大鼠中生成更复杂、更合适的疾病模型,这些模型可以概括人类肾脏病理的关键方面。这些进展最终将用于识别具有更大临床相关性的新治疗方法和治疗靶点。