17 beta-Estradiol prevents mesenteric injury induced by occlusion of the proximal descending aorta in male rats

Autor(es)

Rocha de Sousa, Paulo Thales ^[1] ; Breithaupt-Faloppa, Ana Cristina ^[1] ; Correia, Cristiano de Jesus ^[1] ; Simao, Raif Restivo ^[1] ; Ferreira, Sueli Gomes ^[1] ; Fiorelli, Alfredo Inacio ^[1] ; Pinho Moreira, Luiz Felipe ^[1] ; Sannomiya, Paulina ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Med Sch, Heart Inst InCor, LIM 11, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF VASCULAR SURGERY; v. 67, n. 2, p. 597-606, FEB 2018.
• Citações Web of Science: 5

Resumo

Objective: In surgical aortic repair or cardiac surgery with aorta occlusion, the occurrence of mesenteric ischemia and bowel injury has been associated with higher short-term mortality. The vascular protection of estrogens has been investigated and is mainly mediated by increasing the availability of nitric oxide (NO). Therefore, this study investigated the role of 17 beta-estradiol on visceral ischemia-reperfusion (I/R) injury after descending aorta occlusion in male rats. Methods: Mesenteric ischemia was induced in male Wistar rats by placing a 2F Fogarty arterial embolectomy catheter (Edwards Lifesciences, Irvine, Calif) in the descending aorta, which remained occluded for 15 minutes, followed by reperfusion for up to 2 hours. Rats were divided into four groups: (1) rats that underwent surgical manipulation only (sham, n = 22); (2) rats that underwent I/R injury (n = 22); (3) rats treated with intravenous 17b-estradiol (280 mu g/kg) 30 minutes before I/R (n = 22); (4) or at the beginning of reperfusion (n = 22). Intestinal histopathologic changes were evaluated by histomorphometry. Mesenteric microcirculatory alterations were assessed by laser Doppler flowmetry and intravital microscopy technique. Protein expression of intercellular adhesion molecule-1, P-selectin, endothelial NO synthase (eNOS), and endothelin-1 was evaluated by immunohistochemistry; in addition, eNOS and endothelin-1 gene expressions were quantified by real-time polymerase chain reaction. Serum cytokines were measured by enzyme-linked immunosorbent assay. Results: Relative to the sham group, the I/R group exhibited a highly pronounced loss of intestine mucosal thickness, a reduction in mesenteric blood flow (P=.0203), increased migrated leukocytes (P <.05), and high mortality rate (35%). Treatment with 17 beta-estradiol before aorta occlusion preserved intestine mucosal thickness (P = .0437) and mesenteric blood flow (P=.0251), reduced the number of migrated leukocytes (P <.05), and prevented any fatal occurrence. Furthermore, 17 beta-estradiol downregulated the expression of intercellular adhesion molecule-1 (P=.0001) and P-selectin (P <.0001) on the endothelium and increased the protein expression of eNOS (P <.0001). The gene expressions of eNOS and endothelin-1 did not differ between the groups. Conclusions: The prophylactic treatment with 17 beta-estradiol showed better overall repercussions and was able to prevent any fatal occurrence, increase eNOS expression, thus preserving mesenteric perfusion and intestinal integrity, and reduce inflammation. Clinical Relevance: The results of this study show that 17b-estradiol might be a supplementary approach to prevent mesenteric ischemia and intestinal bowel injury caused by major surgical procedures, particularly when aortic clamping is involved. (AU)

• Processo FAPESP: 13/02563-2 - Avaliação dos efeitos do 17beta-estradiol na lesão mesentérica pela oclusão da porção supracelíaca aórtica em ratos machos
• Beneficiário: Paulina Sannomiya
• Modalidade de apoio: Auxílio à Pesquisa - Regular