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Nrf2 and Snail-1 in the prevention of experimental liver fibrosis by caffeine

World Journal of Gastroenterology 2013年第47期19卷 9020-9033页

作者： Daniela Gordillo-Bastidas Edén Oceguera-Contreras Adriana Salazar-Montes Jaime González-Cuevas Luis Daniel Hernández-Ortega Juan Armendáriz-Borunda nstitute of Molecular Biology in Medicine and Gene Therapy/CUCS University of GuadalajaraGuadalajaraJalisco 44100México

AIM:To determine the molecular mechanisms involved in experimental hepatic fibrosis prevention by caffeine(CFA).METHODS:Liver fibrosis was induced in Wistar rats by intraperitoneal thioacetamide or bile duct ligation and they were concomitantly treated with CFA(15 mg/kg per day).Fibrosis and inflammatory cell infiltrate were evaluated and classified by Knodell *** infiltrate was quantified by immunohistochemistry(anti-CD11b).Gene expression was analyzed by quantitative reverse transcription-polymerase chain reaction for collagenⅠ?(Col-1),connective tissue growth factor(CTGF),transforming growth factorβ1(TGF-β1),tumor necrosis factor alpha(TNF-α),interleukin-1(IL-1),IL-6,superoxide dismutase(SOD)and catalase(CAT).Activation of Nrf2 and Snail-1 was analyzed by ***-αexpression was proved by enzyme-linked immunosorbant assay,CAT activity was performed by ***:CFA treatment diminished fibrosis index in treated *** Knodell index showed both lower fibrosis and *** of profibrogenic genes CTGF,Col-1 and TGF-β1 and proinflammatory genes TNF-α,IL-6 and IL-1 was substantially diminished with CFA treatment with less CD11b positive *** lower values of transcriptional factor Snail-1 were detected in CFA treated rats compared with cirrhotic rats without treatment;in contrast Nrf2was increased in the presence of *** of SOD and CAT was greater in animals treated with CFA showing a strong correlation between mRNA expression and enzyme ***:Our results suggest that CFA inhibits the transcriptional factor Snail-1,down-regulating profibrogenic genes,and activates Nrf2 inducing antioxidant enzymes system,preventing inflammation and fibrosis.

关键词： Liver fibrosis Caffeine Thioacetamide Bile duct ligation profibrogenic genes Proinflammatory cytokines Antioxidant enzymes

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