Acute lung injury induced by acute uremia and renal ischemic-reperfusion injury: The role of toll-like receptors ۲ and ۴, and oxidative stress

Objective(s): Acute lung injury (ALI) is a common complication of distant organ dysfunction induced by acute kidney injury (AKI). Toll-like receptors (TLRs) have a critical role in progression of AKI. The main goal of this study was to determine whether lung gene expression of TLR۲ and TLR۴ change by ischemic (renal bilateral ischemic-reperfusion; BIR) and uremic (bilateral nephrectomy; BNX) AKI.Materials and Methods: Forty male rats were divided into five groups. Two kidneys were removed in BNX, and renal pedicles were clamped in BIR for ۴۵ min. The kidney and lung tissue, and blood samples were collected and saved after ۲۴ hr in all groups. The bone marrow mesenchymal stem cells were immediately injected (۱×۱۰۶,IV) into the treated groups. The expression of TLR۲, TLR۴, TNF-α, and VEGF was checked by RT-PCR in the tissue samples. MDA level, SOD, and CAT activity were evaluated in the tissue samples.Results: Structural disturbance of ALI was detected as alveolar hemorrhage and vascular congestion after BIR and BNX.  Lung TLR۲ and TLR۴ but not TNF-α and VEGF up-regulated in these groups. Oxidative stress stabilized after the BIR and BNX in the tissue samples. BMSCs reduce the expression of TLR۲ and TLR۴ and oxidative stress in the treated groups. Conclusion: Acutely gathering systemic mediators after renal ischemic or uremic injury induce ALI through overexpression of TLR۲ and TLR۴ and oxidative stress. Therefore, the Lung protective effect of BMSCs may be related to modulation of TLR۲ and TLR۴ and oxidative stress in the kidney and lung tissue.

Keywords:

Acute lung injury , Acute kidney injury , bone marrow , Inflammation , Mesenchymal stem cell , Oxidative stress , Pattern recognition receptors