Influnence Of Vacuum-Assisted Closure On Chronic Wound Healing With Angiogenesis, Secretion Peripheral Neuropeptides, Apoptosic Modulation Related Gene Expression

. The management of chronic and nonhealing wounds places an enormous drain on healthcare resources. The increasing number of patients with chronic wounds represents the challenge of new treatments that offer renewed hope to patients with chronic and nonhealing wounds. In 1995, the Food and Drug Administration (FDA) approved Negative pressure wound therapy (NPWT) for the treatment of nonhealing wounds. In January 2000, the FDA expanded the indications for Vacuum-Assisted Closure (NPWT) including chronic, acute, traumatic, subacute, and dehisced wounds, diabeticulcers, pressure ulcers, flap, and grafts. Since 1997, our departentment have applied the vacuum-assisted closure on chronic and nonhealing wounds of human and made lots of research on it. The aim of this study are to investigate the mechanism and of chronic wound healing process, to demonstratethe the factors that influence the events of the wound healing cascade, to explore the mechanism of vacuum-assisted closure on chronic and nonhealing wounds. This study should be a strong theoretical basis for development and justfing the vacuum-assisted closure technique on chronic and nonhealing wounds.Firstly, Our investigations are focused on the denervation chronic wound healing cascades of angiogenesis, distribution and secretion of peripheral neuropeptides, the cellular proliferation and apotosis on histocytes of tissue regeneration, by establishing the animal model of Sprague-Dawley rat denervation chronic wound on which performed that of transmission electron microscopy, Immunohistochemistry , Immunofluorescence, hybridization in situ , western blot ,and rt-PCR technique.Wetestified that the denervation chronic wound exhibited delayed healing related to more events with a series of complex intricated interaction overlapping of angiogenesis, peripheral neuropeptides, cellular proliferation and apotosis than normal wounds ,elc. In contrast with the controls, it is very impotant that we demonstrated the vacuum-assisted closure on chronic and nonhealing wounds (1) promote angiogenesis includeing increased vascular endothelial cell proliferation, the morphologic change, and secretion, meanwhile the expression of vascular endothelial growth factor, CD34 and VEGFmRNA strongly ( P < 0.05). (2)change the distrbution and secretion of peripheral neuropeptides including the expression of calcitonin-gene-related peptide, substance P,nerve growth factor, and NGFmRNA more stronger than controls. ( P < 0.05) (3) change the balance of cellular proliferation and apoptosis including increased the the expression P53,Bd-2 and PCNA in repair cells ( P < 0.05 ) .Secondly, we observed the change of repair cells on expression of the apoptosic modulation related protein and proliferative activity in chronic and nonhealing wound edges of human after vacuum-assisted closure treatment. The research results showed that expression of apoptosic protein P53 and Bcl-2 were much more stronger, Expression of Fas , Ba\ was much more weaker ,the amount of AgNORs was raised than that of before VAC treatment at all check time points.The results of animal and clinical experiment demonstrated the mechnism of passitive healing process and the mechnism of the promoting active healing process after vacuum-assisted closure treatment on the chronic and nonhealing wound. It was comfirmed that vacuum-assisted closure treatment has the effect of transferring the passitive healing process to active healing process on the chronic and nonhealing wound, which suggest that vacuum-assisted closure treatment must be a key component in accelerating the process of wound healing.