Estudo dos efeitos do bloqueio da integrina αvβ3 por uma desintegrina RGD recombinante na cicatrização de hérnia incisional em ratos

Abstract

Introduction: Incisional hernia (IH) is considered a connective tissue disease characterized by defective wound healing process, and it is found in high incidence after abdominal surgeries. Previous studies have shown that DisBa- 01 presents high-affinity to &#945;v&#946;3, which can have wide therapeutic application and/or laboratorial in disorders related to collagen. Hypothesis: Considering the regulatory role of the vitronectin receptor, the &#945;v&#946;3 integrin, in wound healing, we hypothesized that blocking this integrin would affect tissue repair. Objectives: To evaluate the DisBa-01 (a desintegrin RGD-recombinant by snake venom of Bothrops Alternatus) as a blockage of &#945;v&#946;3 integrin on improvement of HI healing. Methods: IH was successfully induced in rats of Sham and DisBa-01 group. DisBa-01 group were treated with different doses (0.25; 0.5 and 1.0 mg/kg). A control group without surgery was included to analyze the surgery effects. Were evaluated the histology, zymography and gene expression of MMP-2, type I and III collagen and VEGF. Type 1A collagen were analysed by Western Blotting. Results: After 14 days, the presence of IH and hernia ring were observed in all sham-operated animals; in contrast, 100% of animals treated with 0.25 and 1.0 mg/kg of Disba-01 did not present visible signals of hernia and showed closed hernia rings. The surgery procedure strongly activated MMP-2 gene expression as well as its activity (P<0.05). Up-regulation of collagen 1 (col-1) and 3 (col-3) gene expression was also observed, DisBa-01 reduced the expression of col-I, however, did not affect col-III, while VEGF expression was down regulated at day14. In contrast, DisBa-01 significantly inhibited MMP-2 gene expression and its activity. Western Blotting analysis revealed the presence of Type1A collagen in all groups, however only DisBa-01 differed statistically of Control group. The thickness of the collagen layer in each of control group presented reduced. However, Sham and DisBa-01, there was a relative increase in all studied animals (P<0.05). Conclusion: These results indicate that &#945;v&#946;3 integrin has an important role in the control of wound healing and its blockade modulate repair conditions, including IH. This information may be especially helpful for patients with recurrent IH.