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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Acid-Base Equilibrium, Animals, Apoptosis, Caspase 3, Caspase Inhibitors, Cryopreservation, Graft Survival, Kidney, Kidney Transplantation, Models, Animal, Organ Preservation Solutions, Oxygen Consumption, RNA, Small Interfering, Reperfusion, Reperfusion Injury, Swine, Warm Ischemia.
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Does naked small interfering RNA of caspase-3 in preservation solution and autologous blood perfusate protect isolated ischemic porcine kidneys? Context: Ischemia-reperfusion injury (IRI) plays key roles in graft viability and posttransplantation function. Caspase-3 associated with apoptosis and inflammation is up-regulated by IRI. We propose that naked small interfering RNA (siRNA) targeting caspase-3 may prevent IRI and improve kidney preservation. Porcine kidneys were retrieved after 10-min warm ischemia and flushed with 500 mL hyperosmolar citrate. Caspase-3 siRNA was administered directly into the renal artery in hyperosmolar citrate solution (3 μg/ml) with the renal vein clamped and into autologous blood (0.15 μg/ml), both of which were stored for 24 hr on ice. The kidneys were reperfused with oxygenated autologous blood for 3 hr on an isolated organ perfusion system to assess renal function. In the siRNA-treated group, the expression of 32-kDa caspase-3 precursor and 17-kDa active subunit was down-regulated by 30% and 56%, respectively, with 40% reduction in active caspase-3+ cells. Consequently, apoptotic cells in the renal cortex were significantly decreased by 47%, whereas inflammatory cells were only marginally reduced by 26%. Caspase-3 siRNA also doubled oxygen consumption and significantly neutralized perfusate pH. Renal blood flow was gradually increased from 5 min to 3 hr by caspase-3 siRNA and marginally improved at the end of 3-hr reperfusion by 45%.
assistant
The administration of caspase-3 siRNA directly into the kidney and hemoperfusate during cold preservation improved IRI with reduced caspase-3 and apoptosis, and better renal oxygenation and acid-base homeostasis. This proof of principle experiment using a novel siRNA therapy in large animal organs provides valuable data for human kidney transplantation. Final Decision: yes