c-FLIPL在肝纤维化形成与逆转中的表达变化与功能研究

Objective The purposes of this study were to investigate the characteristics and implication of c-FLIPL in the process of formation and recovery of hepatic fibrosis. Methods The models induced by CCl4 for 12 weeks and spoatntaneous resolution for 4 weeks. HSCs of different periods were isolated from normal male SD rats by sequential in situ perfusion with collagenase and protease. The mRNA and protein expressions of c-FLIPL were determined by RT-PCR and Western blot. Interference by siRNA to test the expression of c-FLIPL and the apoptosis rate of HSC. Results compared with the liver fibrosis model group, resolution rats' ALT, AST were significantly lower, the serum index of liver fibrosis (HA, HA, LN, PC Ⅲ, C Ⅳ) and histological index of hydroxyproline content (Hydroxyproline, Hyp) also significantly reduced; histopathological analysis showed that the content of collagen in liver tissue decreased in the process of resolution, meanwhile the extent that collagen fibers extending to tissue were also significantly reduced. In the immunohistochemical detection of α-SMA which is the marker of the active HSC, the quantity of active HSC was significantly decreased in the liver tissue of resolution comparing to model group. The expressions of c-FLIPL in liver tissue and HSC were significantly reduced comparing with model group. Interference by siRNA to test the expression of c-FLIPL model group, the apoptosis rate of HSC induced was significantly increased. Conclusion These results suggested that the expression change of c-FLIPL at different stages of liver fibrosis influnced the apoptosis sensitivity of HSC induced by TRAIL.