Abstract
Intestinal anastomosis is a routine procedure in pediatric surgery, with leakage being a significantcomplication. Human alpha1-antitrypsin (AAT), whose physiological serum concentrations range from 0.9-2.0 mg/ml,is known to accelerate wound healing and stimulate the expression of cell proliferation-related genes. Wehypothesized that AAT might enhance anastomotic healing. In a monolayer of non-tumorigenic HIEC-6 epithelial cells derived from fetal intestine a scratch wascreated. Standard medium without (control) or with AAT (0.5 and 1 mg/ml) was added. Cells were observed using aLife-Cell Imaging System. Cell proliferation was assessed, and the expression of proliferation-related genes wasmeasured by qRT-PCR. In the presence of AAT, the scratch closed significantly faster. Cells treated with 1 mg/ml AAT showed 53%repopulation after 8 h and 97% after 18 h, while control cells showed 24% and 60% repopulation, respectively(p < 0.02). The treatment with AAT induced HIEC-6-cell proliferation and significantly increased the mRNA-expressionof CDKN1A, CDKN2A, ANGPTL4, WNT3 and COL3A1 genes. AAT did not change the mRNA-expression of CXCL8 butdecreased levels of IL-8 as compared to controls. At physiological concentrations AAT accelerates the confluence of intestinal cells and increases cellproliferation. The local administration of AAT may bear therapeutic potential to improve anastomotic healing.
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