Investigation Of The Effect Of Hirudin On The Promotion Of Blood Supply And Angiogenesis In Rat Ischemic Skin Flap

Objective Mechanistic study of the effect of hirudin on perfusion and angiogenesis in distal ischemic skin flap tissues.Method Two random dorsal skin flaps of 2cm×8cm were made on individual SD rat and assigned randomly to hirudin treatment and control groups.Each flap received daily subcutaneous injection of either 0.5 U hirudin at proximal,middle and distal areas during days 0-3 in hirudin treatment group or the same amount of saline in control group.The distal flap tissue perfusion,microvessel density(MVD)of flap biopsies,protein expression levels of vascular endothelial growth factor(VEGF)and thrombospondin-1(TSP-1)at different time intervals were detected by a Full-Field Laser Perfusion Imager,immunohistochemistry and Western Blot,respectively.The flap survival areas at day 6 were also measured.Results In comparison with control,injection of hirudin resulted in enhanced distal flap perfusion since day 1(P<0.01),higher MVD at day 4(P<0.01)and significant upregulation of flap tissue VEGF levels during days 1-6(P<0.05).The tissue expression levels of TSP-1 of hirudin group were significantly lower at days 1-4(P<0.01)than that of control group.Larger meanflap survival area was observed in hirudin treatment group(P<0.01).Conclusions Hirudin improves ischemic skin tissue survival through enhancing the recovery of perfusion,regulating angiogenesis associated factors,and facilitating microvessel formation in ischemic flap tissue.