Characteristics And Mechanisms Of Tubular Cell Apoptosis Induced By Renal Ischemia/reperfusion Injury In Aged Rats

Background Acute renal failure (ARF) secondary to renal ischemia/ reperfusion (I/R) injury is a frequent clinical problem. Susceptibility to ischemic ARF in the elderly is more common, while the mechanisms are currently unknown yet. Tubular cell apoptosis accounts for a significant component of renal dysfunction in ARF. Dysregulation of apoptosis is also associated with the aging process. Aged rats exhibited enhanced tubular cell apoptosis compared with young ones in physiological conditions. However, whether apoptosis is increased in aged animals with renal I/R injury and its role in the ischemic ARF are unclear yet. Objective We investigated the characteristics of tubular cell apoptosis induced by renal ischemia/reperfusion injury in aged rats. We studied caspase-dependent intrinsic (mitochondrial) and extrinsic (death receptor) pathways, and furthermore, interfered the two ways using cyclosporine A (CsA) and mycophenolate mofetil (MMF), respectively, to explore the pathway(s) responsible for the age-related differences. Methods The aged (27 months) and young (3 months) male Wistar rats underwent bilateral renal artery occlusion for 30 min to induce renal ischemia. Rats were pretreated with normal saline, CsA or MMF. Age-matched sham-operated rats served as controls. Rats were sacrificed at 18 h of reperfusion. Serum creatinine (SCr) level, renal morphology changes, tubular cell apoptosis, mRNA level of renal caspase-3, 8, 9, Bcl-2, Bax and Fas, protein expression of cytosolic cytochrome c, caspase-3, 8 and 9 as well as renal malondialdehyde (MDA) content and Superoxide...