Autophagy is involved in the activation of hepatic stellate cells (HSCs), which is the key process of liver fibrosis. We reasoned that chloroquine, based on its ability to inhibit autophagy, might exert beneficial effects in liver fibrosis. Liver fibrosis in rats was induced by carbon tetrachloride (CCl 4 ). Rats were divided into three groups, a normal control group (N group), model group (M group), and chloroquine group (CQ group). Liver fibrosis in the rats was evaluated by hematoxyline-eosin (H&E) and Masson staining. The activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TB) were determined using an automated biochemistry analyzer. Total hepatic hydroxyproline levels were determined with a kit. The expressions of α-smooth muscle actin (α-SMA) and transforming growth factor-β1 (TGF-β1) were detected by immunofluorescence staining, and the expressions of LC3-II and p62 were determined by Western blotting. Compared with N group, M group showed impaired liver function, liver fibrosis, increased hydroxyproline content, up-regulated expressions of α-SMA and TGF-β1, which have been reported to be pro-fibrogenic genes in vivo, and increased autophagy flux as indicated by the accumulation of LC3-II and degradation of p62. These changes were attenuated by chloroquine treatment. Chloroquine exerts beneficial effects in CCl 4 -induced liver fibrosis. The mechanism of action includes inhibition of autophagy pathways and inhibition of activation of HSCs.Key words chloroquine; liver fibrosis; autophagy; hepatic stellate cell Hepatic fibrosis, characterized by excessive scar formation due to overproduction and deposition of the extracellular matrix, is the common response to chronic liver injury, ultimately leading to cirrhosis. This process usually occurs over a long period of time and can lead to organ dysfunction and death.
1)Activation of hepatic stellate cells (HSCs) is considered to play a major role in the occurrence and development of hepatic fibrosis.2) Insights into mechanisms regulating HSC activation are considered as key targets for the treatment of hepatic fibrosis.Autophagy, a highly evolutionarily energy-dependent process implicated as a cell death mechanism, degrades and recycles subcellular organelles.3) During autophagy, the cytoplasmic form LC3-I is processed and recruited to phagophores, where LC3-II is generated by site-specific proteolysis and lipidatio at the C-terminus. Thus this characteristic conversion from endogenous LC3-I to LC3-II can be used to monitor autophagic activity. Recent studies suggest that autophagic flux is increased during HSC activation, and in vitro study have showed that treatment with an autophagy inhibitor partly inhibited HSC activation.4,5) Hence, treatment with an autophagy inhibitor could be a potential new therapeutic strategy for hepatic fibrosis.Chloroquine (CQ), an autophagy inhibitor, is a commonly used therapeutic agent in skin disorders. Growing evidence also suggest that CQ could be useful in fibroblastic d...