Surgical trauma is associated with renal immune cell activation in rats: A microarray study

Acute kidney injury (AKI) is a common perioperative complication that is associated with increased mortality. This study investigates the renal gene expression in male Long-Evans rats after prolonged anesthesia and surgery to detect molecular mechanisms that could predispose the kidneys to injury upon further insults. Healthy and streptozotocin diabetic rats that underwent autoregulatory investigation in an earlier study were compared to rats that were sacrificed quickly for mRNA quantification in the same study. Prolonged surgery caused massive changes in renal mRNA expression by microarray analysis, which was validated by quantitative real-time PCR with good correlation. Furthermore, bioinformatics analysis using gene ontology and pathway analysis identified biological processes involved in immune system activation, such as immune system processes (p = 1.3 × 10^-80 ), immune response (p = 1.3 × 10^-60 ), and regulation of cytokine production (p = 1.7 × 10^-52 ). PCR analysis of specific cell type markers indicated that the gene activation in kidneys was most probably macrophages, while granulocytes and T cell appeared less activated. Immunohistochemistry was used to quantify immune cell infiltration and showed no difference between groups indicating that the genetic activation depends on the activation of resident cells, or infiltration of a relatively small number of highly activated cells. In follow-up experiments, surgery was performed on healthy rats under standard and sterile condition showing similar expression of immune cell markers, which suggests that the inflammation was indeed caused by the surgical trauma rather than by bacterial infection. In conclusion, surgical trauma is associated with rapid activation of immune cells, most likely macrophages in rat kidneys.