OBJECTIVETo study the proliferation and apoptosis in carbon tetrachloride induced rat liver fibrosis.

METHODSWistar rats were injected subcutaneously with 40% CCl4-olive oil twice weekly for 12 weeks. Liver tissues were obtained at the end of 4, 8, 12 and 16 weeks for histological examination, hydroxyproline (Hyp) assay and proteomic analysis. After two dimension electrophoresis (2-DE), the silver stained gels were analyzed with PDQUEST 2-DE. More than 30 differentially expressed proteins were identified by MALDI-TOF-MS.

RESULTSThe degree of collagen deposition and hydroxyproline content of the fibrotic livers increased continuously during the 12 weeks of CCl4 administration, peaked at the end of week 12 (P < 0.05) and declined significantly at week 16 (P < 0.05). Significant differences were observed in two parameters at each time point between the control and the model group. Meanwhile, dramatic change of hepatic proteome in the model group rats was also seen. Differentially expressed proteins identified by MALDI-TOF-MS were categorized as proliferation-related proteins/enzymes (proliferating cell nuclear antigen p120, p40 and cyclin F ubiquitin-conjugating enzyme 7 UBC7), and apoptosis-related proteins, mainly caspase-12 which was absent in the control rats.

CONCLUSIONProliferation and apoptosis related proteins are expressed dynamically in different stages of rat liver fibrosis induced by CCl4.