Humes H D, Lake E W, Liu S
University of Michigan, Ann Arbor, USA.
Miner Electrolyte Metab. 1995;21(4-5):353-65.
Experimental data suggests the recovery of renal function after ischemic or nephrotoxic acute renal failure is due to a replicative repair process dependent upon predominantly paracrine release of growth factors. These growth factors promote renal proximal tubule cell proliferation and a differentiation phase dependent on the interaction between tubule cells and basement membrane. These insights identify the molecular basis of renal repair and ischemic and nephrotoxic acute renal failure, and may lead to potential therapeutic modalities that accelerate renal repair and lessen the morbidity and mortality associated with these renal disease processes. In this regard, there is a prominent vasoconstrictor response of the renal vasculature during the postischemic period of developing acute renal failure. The intravenous administration of pharmacologic doses of atrial natriuretic factor (ANF) in the postischemic period have proven efficacious by altering renal vascular resistance, so that renal blood flow and glomerular filtration rate improve. ANF also appears to protect renal tubular epithelial integrity and holds significant promise as a therapeutic agent in acute renal failure. Of equal or greater promise are the therapeutic interventions targeting the proliferative reparative zone during the postischemic period. The exogenous administration of epidermal growth factor or insulin-like growth factor-1 in the postischemic period have effectively decreased the degree of renal insufficiency as measured by the peak serum creatinine and has hastened renal recovery as measured by the duration of time required to return the baseline serum creatinine values. A similarly efficacious role for hepatocyte growth factor has also been recently demonstrated.
实验数据表明，缺血性或肾毒性急性肾衰竭后肾功能的恢复归因于一种复制性修复过程，该过程主要依赖旁分泌释放生长因子。这些生长因子促进肾近端小管细胞增殖以及依赖于小管细胞与基底膜之间相互作用的分化阶段。这些见解确定了肾修复以及缺血性和肾毒性急性肾衰竭的分子基础，并可能带来加速肾修复以及降低与这些肾脏疾病过程相关的发病率和死亡率的潜在治疗方式。在这方面，在急性肾衰竭发展的缺血后时期，肾血管系统存在显著的血管收缩反应。在缺血后时期静脉注射药理剂量的心钠素（ANF）已被证明通过改变肾血管阻力是有效的，从而使肾血流量和肾小球滤过率得以改善。ANF似乎还能保护肾小管上皮的完整性，并且作为急性肾衰竭的治疗药物具有很大的前景。同样或更有前景的是在缺血后时期针对增殖性修复区域的治疗干预。在缺血后时期外源性给予表皮生长因子或胰岛素样生长因子-1已有效地降低了以血清肌酐峰值衡量的肾功能不全程度，并通过恢复至基线血清肌酐值所需的时间长度衡量加速了肾恢复。最近也已证明肝细胞生长因子具有类似的有效作用。
