Identification of novel mechanisms of silymarin on the carbon tetrachloride-induced liver fibrosis in mice by nuclear factor-魏B bioluminescent imaging-guided transcriptomic analysis

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• 作者：Chia-Cheng Li^a ; Chien-Yun Hsiang^b ; Shih-Lu Wu^c ; Tin-Yun Ho^a ; ^d ; ^{cyhsiang@mail.cmu.edu.tw}
• 关键词：CCl4 ; carbon tetrachloride ; Cox ; cytochrome c oxidase ; GAPDH ; glyceraldahyde-3-phosphate dehydrogenase ; H&E ; hematoxylin and eosin ; NF-魏B ; nuclear factor-魏B ; 伪-SMA ; 伪-smooth muscle actin ; TGF-尾 ; transforming growth factor-尾
• 刊名：Food and Chemical Toxicology
• 出版年：2012
• 期刊代码：20_02786915
• 类别：pha
• 出版时间：May, 2012
• 卷：50
• 期：5
• 页码：1568-1575
• 文件大小：1270 K

摘要

In this study, we applied bioluminescent imaging-guided transcriptomic analysis to evaluate and identify the therapeutic potentials and novel mechanisms of silymarin on carbon tetrachloride (CCl₄)-induced liver fibrosis. Transgenic mice, carrying the luciferase genes driven by nuclear factor-魏B (NF-魏B), were given with CCl₄ and/or silymarin. In vivo NF-魏B activity was evaluated by bioluminescent imaging, liver fibrosis was judged by Sirius red staining and immunohistochemistry, and gene expression profiles of silymarin-treated livers were analyzed by DNA microarray. CCl₄ enhanced the NF-魏B-dependent hepatic luminescence and induced hepatic fibrosis, while silymarin reduced the CCl₄-induced hepatic luminescence and improved CCl₄-induced liver fibrosis. Microarray analysis showed that silymarin altered the transforming growth factor-尾-mediated pathways, which play pivotal roles in the progression of liver fibrosis. Moreover, we newly identified that silymarin downregulated the expression levels of cytoskeleton organization genes and mitochondrion electron-transfer chain genes, such as cytochrome c oxidase Cox6a2, Cox7a1, and Cox8b genes. In conclusion, the correlation of NF-魏B-dependent luminescence and liver fibrosis suggested the feasibility of NF-魏B bioluminescent imaging for the evaluation of liver fibrosis progression and therapeutic potentials. Moreover, our findings suggested that silymarin might exhibit anti-fibrotic effects in vivo via altering the expression of genes involved in cytoskeleton organization and mitochondrion electron-transfer chain.