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DNLA-dependent activation of Nrf2 pathway protects against CCl4-induced mouse acute liver injury

Shiyue Li  Qian Zhou  Chun-xia Li  Yuan-fu Lu  Yan-liu Lu  Shang-fu Xu  Jing-shan Shi  Shao-yu Zhou  Jie Liu  Qin Wu  
【摘要】:The present study aim to investigate the protective effects of Dendrobium nobile Lindl Alkaloids(DNLA) on CC14 induced acute liver injury,and explore whether DNLA-mediated liver protection is relevant to nuclear factor erythroid-2-related factor 2(Nrf2) signaling pathway.C57 BL/6 mice were randomly divided into four groups(n=10):control,model(0.2%CC14,0.1 ml·10 g-1),CC14+DNLA(10 mg/kg),and CC14+DNLA(20 mg/kg).DNLA was administrated by oral gavage for 7 day.After 7 days,0.2 % CC14 was given by intraperitoneal injection once to establish the acute liver injury model.The effect of DNLA on acute liver injury was assessed by detecting alanine aminostransferase(ALT) and aspartate aminotransferase(AST) activity in mouse serum,and examining the morphological and ultrastructural changes of liver tissue;RT-PCR was used to determine the gene expression level of Nrf2,Quinone oxidoreductase 1(Nqo1),and Hemeoxygenese(HO-1) in liver tissue;Western blot was used to determine the protein expression level of nuclear and cytoplasmic Nrf2,Nqol and HO-1 in liver tissue;The contents of malondialdehyde(MDA) and superoxide dismutase(SOD) activity in liver tissue were measured using commercial assay kits.As a result,DNLA significantly reduced the enhanced activities of AST and ALT in serum caused by CC14.Moreover,we observed that DNLA improved CC14-induced liver tissue injury and impaired liver mitochondrial respiration.In additional,DNLA decreased content of MDA in liver tissue(P0.05),and increased the activity of SOD liver tissue of mice treated with CC14(P0.05).Finally,DNLA significantly increased the expression of Nrf2,NQO1 and HO-1 mRNA level in liver tissue,and increased the expression of nuclear Nrf2 protein,and Nqol and HO-1 proteins in liver tissue(P0.05).Taken together,DNLA has protective effect on CC14-induced acute liver injury in mice,and its mechanism is relevant to activation of Nrf2 signaling pathway in liver tissue.

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