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• W2904955186 abstract "Background . To evaluate the AMP-activated protein kinase- (AMPK-) mediated signaling and NF- κ B-related inflammatory pathways that contribute to cholestatic diseases in the bile duct ligation (BDL) rat model of chronic cholestasis and verify the protective role of 5-Aminoimidazole-4-carboxamide1- β -D-ribofuranoside (AICAR) against hepatic injury and fibrosis triggered by cholestasis-related inflammation. Methods . Animals were randomly divided into three groups: sham-operated group, BDL group, and BDL+ AICAR group. Cholestatic liver injury was induced by common BDL. Two weeks later, rats in BDL+AICAR group started receiving AICAR treatment. Hepatic pathology was examined by haematoxylin and eosin (H&E) and sirius red staining and hydroxyproline assay was performed in evaluating the severity of hepatic cirrhosis. Real-time PCR and Western blot were performed for RNA gene expression of RNA and protein levels, respectively. Results . The BDL group showed liver injury as evidenced by histological changes and elevation in serum biochemicals, ductular reaction, fibrosis, and inflammation. The mRNA expression of canonical NF- κ B inflammatory cytokines such as TNF- α , IL-1 β , TGF- β , and the protein of noncanonical NF- κ B, P100, and P52 was upregulated in the livers of BDL rats. The BDL rats with the administration of AICAR could induce AMPK activation inhibiting the noncanonical NF- κ B pathway to attenuate liver injury and fibrosis in BDL rats. Conclusion . The BDL model of hepatic cholestatic injury resulting in activation of Kupffer cells and recruitment of immune cells might initiate an inflammatory response through activation of the NF- κ B pathway. The AMPK activator AICAR significantly alleviated BDL-induced inflammation in rats by mainly inhibiting the noncanonical NF- κ B pathway and thus protecting against hepatic injury and fibrosis triggered by BDL." @default.
• W2904955186 created "2018-12-22" @default.
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• W2904955186 date "2018-12-19" @default.
• W2904955186 modified "2023-10-18" @default.
• W2904955186 title "AICAR-Induced AMPK Activation Inhibits the Noncanonical NF-<mml:math xmlns:mml=http://www.w3.org/1998/Math/MathML id=M1><mml:mrow><mml:mtext mathvariant=bold>κ</mml:mtext></mml:mrow></mml:math>B Pathway to Attenuate Liver Injury and Fibrosis in BDL Rats" @default.
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• W2904955186 doi "https://doi.org/10.1155/2018/6181432" @default.
• W2904955186 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6314002" @default.
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