Inhibitory effects of rapamycin on the different stages of hepatic fibrosis

Figure 1 Comparison of histological findings between the groups that underwent bile duct ligation (BDL) with/without rapamycin treatment and the control. A: Hematoxylin and eosin (HE) staining. The bile duct ligation (BDL)⁺/Rapa⁺⁺ group showed the smallest expansion of portal areas, with the least amount of ductular proliferation and the most mild inflammatory reaction among the BDL groups; B: Masson-Trichrome staining. The BDL⁺/Rapa⁺⁺ group showed the lowest degree of fibrotic septa formation and deposition of collagen among BDL groups (blue); C: α-smooth muscle actin (α-SMA) staining (dark brown). The BDL⁺/Rapa⁺⁺ group showed the lowest amount of staining among BDL groups; D: Cytokeratin 19 (CK 19) protein expression (dark brown). The BDL⁺/Rapa⁺⁺ group showed the lowest amount of staining among BDL groups. Rapa: Rapamycin; Rapa⁺: Rat administered rapamycin for 28 d from the 14^th day post-BDL; Rapa⁺⁺: Rat administered rapamycin for 28 d beginning the first day post-BDL. Original magnification: × 100(^a-d).

Figure 2 Transforming growth factor β1 and platelet-derived growth factor mRNA expression was assessed by polymerase chain reaction analysis. A: Transforming growth factor β1 (TGFβ1); B: Platelet-derived growth factor (PDGF). BDL: Bile duct ligation; Rapa: Rapamycin; Rapa⁺: Rat administered rapamycin for 28 d starting the 14^th day after BDL; Rapa⁺⁺: Rat administered rapamycin treatment for 28 d starting the 1^st day after BDL; GAPDH: Glyceraldehyde 3-phosphate dehydrogenase. ^aP < 0.05 vs other group; ^cP < 0.05 vs BDL⁺/Rapa⁺⁺ group.

Figure 3 Western blot analysies showed the p70s6k and p-p70s6k expression levels in the advanced liver fibrosis samples. A: 70-kDa ribosomal S6 kinase (p70s6k); B: p-p70s6k. BDL: Bile duct ligation; Rapa: Rapamycin; Rapa⁺: Rat administered rapamycin for 28 d beginning the 14^th day post-BDL; Rapa⁺⁺: Rat administered rapamycin for 28 d beginning the first day post-BDL. ^aP < 0.05 vs other group; ^cP < 0.05 vs BDL⁺/Rapa⁺ group; ^eP < 0.05 vs BDL⁺/Rapa^- group.