Hydrogen sulfide treatment ameliorates long-term renal dysfunction resulting from prolonged warm renal ischemia-reperfusion injury

摘要

Introduction: The incidence of renal cell carcinoma (RCC) continues to rise concurrently with the increased prevalence of end-stage renal disease worldwide. Treatment for small renal masses continues to be partial nephrectomy mostly involving the clamping of renal blood vessels. Although necessary, this technique results in warm renal ischemia and reperfusion injury (IRI) to the afflicted kidney. We have recently demonstrated that hydrogen sulfide (H₂S), a novel endogenous gaseous molecule, protects against prolonged cold and short-term warm renal IRI. In the current study, we examined whether exogenous H₂S has long-term protective effects against warm renal IRI associated with renal surgical procedures. Methods: Uni-nephrectomized Lewis rats underwent 1 hour of warm ischemia induced by clamping of the renal pelvis. Animals underwent either intraperitoneal treatment with phosphate buffered saline (PBS; IRI group) or PBS supplemented with 150 μM NaHS (H₂S group), and were compared against Sham-operated rats. Results: H₂S treatment improved long-term renal function as serum creatinine at day 7 was significantly decreased in the H₂S group compared to IRI animals ( p 2S treatment decreased the expression of pro-inflammatory markers TLR-4, TNF-α, IFNγ, IL-2 and ICAM-1, increased the expression of pro-survival molecule Bcl-2 and decreased the expression of pro-apoptotic marker BID at postoperative day 1. H₂S-treated kidneys also showed a significant decrease ( p 2S treatment improved long-term renal function and decreased long-term inflammation associated with warm IRI, and may offer a novel therapeutic approach to preventing warm IRI-induced renal injury associated with renal surgical procedures.