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An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
Published on: August 13, 2019
PROGESTERONE TREATMENT POSITIVE EFFECTS IN THE FUNCTION AND INFLAMMATION OF INTESTINE COMPROMISED BY AORTIC OCCLUSION
Brunella Valbão Flora Agostinho1, Pedro Luiz Zonta de Freitas, Ivana Ramires Fraga
1Laboratorio de Cirurgia Cardiovascular e Fisiopatologia da Circulação (LIM-11), Instituto do Coração (INCOR), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Abstract:
Aortic surgery induces severe ischemia and reperfusion. Ischemia/reperfusion (I/R) is a critical medical issue due to its high sensitivity tissue damage, inflammation, mucosal injury, and motility impairment. Studies have demonstrated that female sex hormones modulate the inflammatory response triggered by I/R. Progesterone (P4) had positive effects on intestines after trauma. We evaluated the effects of P4 on intestinal function and inflammation in a model of I/R by aortic occlusion. Methods Male Wistar rats were randomized to the following four groups: sham, surgically manipulated; IR, animals subjected to I/R; P4 pre, animals treated with P4 30 min before I/R and P4 post, treated immediately after flow reestablishment. I/R was induced by catheter 2F insufflation in the descending aorta, occluded for 30 min, followed by reperfusion for 2 h. Intestinal function, inflammatory and apoptosis markers, and mesenteric microcirculation were analyzed. Results Aortic occlusion led to systemic changes and intestinal homeostasis disruption. The I/R decreased the gastrointestinal transit (sham 69%, IR 46%, P = 0.0014) and the progesterone reduced impact induced by I/R (IR 46%, P4 post 60%, P = 0.0461). The treatment prevented the increase of epithelial mucosal barrier permeability and edema formation triggered by I/R (sham 0.2770 ng/mL vs. I/R 5.455 ng/mL, P = 0.0048) and (P4 pre 2.027 ng/mL, P = 0.0393). It also reduced inflammatory cell infiltration to intestinal tissue (IR 0.5876 vs. P4 pre 0.1818, P = 0.0003 and P4 post 0.1393 stained area/tissue area, P < 0.0001), modulating the release of inflammatory mediators and apoptosis markers (IR 0.1806 vs. P4 pre 0.0468, P = 0.0452). Conclusion Progesterone treatment was effective in modulating the neutrophil response and other inflammatory markers, decreased apoptosis, and improved gastrointestinal function triggered by I/R.
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