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Antioxidant properties of glutamine and its role in VEGF-Akt pathways in portal hypertension gastropathy

World Journal of Gastroenterology 2013年第28期19卷 4464-4474页

作者： Camila Marques Francielli Licks ingrid zattoni Beatriz Borges Luiz Eduardo Rizzo de Souza Claudio Augusto Marroni Norma Possa Marroni Universidade Federal do Rio Grande do Sul-PPG Fisiologia Porto Alegre 90000100 Brazil Universidade Federal do Paraná Curitiba 81531900 Brazil Departamento de Medicina Interna-Gastroenterologia-Universidade Federal de Ciências da Saúde de Porto Alegre Porto Alegre 90000100 Brazil Universidade Federal do Rio Grande do Sul-PPG Fisiologia Universidade Luterana do Brasil Porto Alegre 90000100 Brazil

AIM: To investigate the effects of glutamine on oxidative/nitrosative stress and the vascular endothelial growth factor (VEGF)-Akt-endothelial nitric oxide synthase (eNOS) signaling pathway in an experimental model of portal hypertension induced by partial portal vein ligation (PPVL). METHODS: Portal hypertension was induced by PPVL. The PPVL model consists of a partial obstruction of the portal vein, performed using a 20 G blunt needle as a guide, which is gently removed after the procedure. PPVL model was performed for 14 d beginning treatment with glutamine on the seventh day. On the fifteenth day, the mesenteric vein pressure was checked and the stomach was removed to test immunoreactivity and oxidative stress markers. We evaluated the expression and the immunoreactivity of proteins involved in the VEGF-Akt-eNOS pathway by Western blotting and immunohistochemical analysis. Oxidative stress was measured by quantification of the cytosolic concentration of thiobarbituric acid reactive substances (TBARS) as well as the levels of total glutathione (GSH), superoxide dismutase (SOD) activity, nitric oxide (NO) production and nitrotyrosine immunoreactivity. RESULTS: All data are presented as the mean ± SE. The production of TBARS and NO was significantly increased in PPVL animals. A reduction of SOD activity was detected in PPVL + G group. In the immunohistochemical analyses of nitrotyrosine, Akt and eNOS, the PPVL group exhibited significant increases, whereas decreases were observed in the PPVL + G group, but no difference in VEGF was detected between these groups. Western blotting analysis detected increased expression of phosphatidylinositol-3-kinase (PI3K), P-Akt and eNOS in the PPVL group compared with the PPVL + G group, which was not observed for the expression of VEGF when comparing these groups. Glutamine administration markedly alleviated oxidative/nitrosative stress, normalized SOD activity, increased levels of total GSH and blocked NO overproduction as well

关键词： Partial portal vein ligation Oxidative stress Glutamine Portal hypertension Rats

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