Sphingosine Kinase-1 Gene Transfer Reduces Postoperative Peritoneal Adhesion In A Rat Model

Objective: The recovery of surgery-damaged mesothelial cell layer is a major process for reducing the formation of postoperative peritoneal adhesions. Sphingosine kinase1 (SPK1) is a known signal molecule in regulation of cell proliferation and migration of various type cells. The purpose of this study was to determine the effect of SPK1 gene transfer on the recovery of damaged mesothelial cell layer and on the postoperative formation of peritoneal adhesions.Methods: Rat mesothelial cells were isolated and characterized by expression of cytokeratin and vimentin. The migration of mesothelial cells was determined by scratch wound motility assay. The cellular SPK1 activity was determined by [γ-³¹P] ATP incorporation. Wistar rats underwent laparotomy with subsequent cecum and uterine horn abrasing by using dry sterile gauze. Rats were randomized to either SPK1 gene transfer or control groups. The animals were sacrificed on postoperative day 14. The formation of adhesions was graded.Results: Adenovirus-mediated SPK1 gene transfer could increase the cellular activity of mesothelial cells, leading to enhanced migration. The adhesion median scores of the control and Ad-SPK1 groups were 2.6 and 0.975 (in the rat cecum model), 1.275 and 0.275 (in the rat uterine horn model), respectively. Adhesion scores of Ad-SPKl groups were significantly lower than that of the control group (P< 0.0001).Conclusion: Adenoviral-mediated SPK1 gene transfer promotes the recovery of surgery-damaged mesothelial cell layer and prevents postoperative peritoneal adhesions.