Protein kinase D1 promotes the survival of random-pattern skin flaps in rats.

ABSTRACT

BACKGROUND: In reconstructive surgery, random skin flaps are commonly used tools to cover skin defects, however, their applicability and size are limited by post-operative complications such as marginal ischemia-reperfusion injury and flap necrosis. Protein kinase D1 (PKD1), a calcium/calmodulin-dependent serine/threonine kinase, is known to induce angiogenesis and has been shown to mitigate ischemia in cardiovascular diseases. However, the role of PKD1 has not been investigated in skin flaps. METHOD: Seventy-five male Sprague-Dawley rats with skin flaps were randomly divided into three groups control, PKD1, and CID755673. Seven days following surgery, we assessed the general view and survival rate of the flap using histological analysis. Laser Doppler and lead oxide/gelatin angiography were used to evaluate microcirculation blood flow. Histopathological changes, neovascularization and microvascular density (MVD). were examined and calculated using microscopy after H&E staining. Protein expression levels were determined using immunoblotting and immunohistochemistry techniques. RESULT: PKD1 significantly improved flap survival by upregulating angiogenic factors VEGF and cadherin5 and increasing antioxidant enzymes SOD, eNOS, and HO1, as well as reducing caspase 3, cytochrome c, and Bax expression, and attenuating IL-1ß, IL-6, and TNF-α. In the PKD1 group, PKD1 increased neovascularization, and blood flow and flap survival areas were larger as compared to the control and CID755673 groups. CONCLUSION: These findings show that PKD1 accelerates angiogenesis, reduces oxidative stress, and impedes apoptosis and inflammation, thus resulting in improved flap survival. Our observations indicated that PKD1 could be a therapeutic target for flap failure treatment.