Abstract
α1-antichymotrypsin (ACT) and its murine homolog spi2 are serine protease inhibitors present in plasma, that are locally up-regulated during wound healing. Ad-spi2 and Ad-ACT expression vectors were constructed to address the biological activity of locally expressed serpins. The condition medium of infected COS-1 cell at 2 d postinfection contained 1.23 ng/ml spi2 and 2.61 ng/ml ACT. Ad-LacZ or Ad-spi2 108 pfu was injected into the sponges after 3 d subcutaneous implantation in rats. Histological analysis showed that overexpression of spi2 improves granulation tissue organization and collagen deposition at d7 implantation. Moreover, overexpression of spi2 increases the contents of tissue DNA (23.8%, p < 0.05) and protein (25.3%, p < 0.05) in sponge implantation model in rats. In incisional wound models in both normal and STZ-induced diabetic rats, Ad-spi2 increases tensile strength by 26%(p = 0.011) and 29%(p = 0.022) as well as Ad-ACT increases by 10.3%(p = 0.037) and 32%(p = 0.004), respectively. In adriamycin-induced wound model in rats, histological analysis displayed less inflammatory cells infiltrating in Ad-ACT injected wound than in Ad-LacZ after 21 d injection of adriamycin. Inflammation enzymes MPO and elastase levels were decreased by 32.3% and 29.2% in Ad-ACT injected wound tissue. Our data concluded that overexpression of spi2 and ACT improves wound healing in rats probably via inflammatory resolution. (Supported by Switch Biotech and the Department of Veterans Affairs)
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