Role of chemokine CXC-ligand 16 in renal ischemia-reperfusion injury in mice

Abstract

Objective To investigate the role of chemokine CXC-ligand 16 (CXCL16) in renal ischemia-reperfusion (I/R) injury in the mice. Methods Twelve healthy male C57BL/6 mice and 12 CXCL16-knockout (CXCL16-KO) mice, aged 8-10 weeks, weighing 20-30 g, were studied.The 12 C57BL/6 mice were randomly divided into 2 groups (n=6 each) using a random number table: C57BL/6 sham operation group (group C-S) and C57BL/6 I/R group (group C-I/R). The 12 CXCL16-KO mice were randomly divided into 2 groups (n=6 each) using a random number table: CXCL16-KO sham operation group (group KO-S) and CXCL16-KO I/R group (group KO-I/R). The right kidney was removed, and the left kidney was exposed, and the renal artery was then clamped for 45 min with atraumatic microclips followed by 24 h reperfusion to establish the model of renal I/R in anesthetized mice.Venous blood samples were taken at 24 h of reperfusion for determination of the serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations.The renal specimens were obtained at 24 h of reperfusion for microscopic examination of the pathological changes, and the damage to the renal tubules was scored.The number of myeloperoxidase (MPO) positive cells (MPO+ cells), F4/80+ cells and CD3+ cells in renal tissues was counted by immunohistochemistry.The expression of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), IL-6, and macrophage inflammatory protein-2 (MIP-2) mRNA in renal tissues was determined by real-time reverse transcriptase polymerase chain reaction. Results Compared with group C-S, the serum BUN and Cr concentrations, renal tubular damage score, and the number of MPO+ , F4/80+ , and CD3+ cells were significantly increased, and the expression of TNF-α, IL-1β, IL-6 and MIP-2 mRNA was significantly up-regulated in group C-I/R (P<0.05). Compared with group KO-S, the serum BUN and Cr concentrations, renal tubular damage score, and the number of MPO+ , F4/80+ , and CD3+ cells were significantly increased, and the expression of TNF-α, IL-1β, IL-6 and MIP-2 mRNA was significantly up-regulated in group KO-I/R (P<0.05). Compared with group C-I/R, the serum BUN and Cr concentrations, renal tubular damage score, and the number of MPO+ , F4/80+ , and CD3+ cells were significantly decreased, and the expression of TNF-α, IL-1β, IL-6 and MIP-2 mRNA was significantly down-regulated in group KO-I/R (P<0.05). Conclusion CXCL16 is involved in the pathophysiological process of renal I/R injury in the mice. Key words: Chemokines, CXC; Kidney; Reperfusion injury