Kim Yun Jeung, Lee Eaum Seok, Kim Seok Hyun, Lee Heon Young, Noh Seung Moo, Kang Dae Young, Lee Byung Seok
Yun Jeung Kim, Eaum Seok Lee, Seok Hyun Kim, Heon Young Lee, Byung Seok Lee, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon 301-721, South Korea.
World J Gastroenterol. 2014 Jun 21;20(23):7452-60. doi: 10.3748/wjg.v20.i23.7452.
To investigate and compare the inhibitory effects of rapamycin in the different stages of liver fibrosis.
We performed bile duct ligation (BDL) in male Wistar rats (n = 24). The experimental rats were classified into four groups: the BDL(+)/Rapa(-) group (un-treated control, n = 4), the BDL(+)/Rapa(+) group (treated 14 d after BDL, n = 8), the BDL(+)/Rapa(++) group (treated on the day after BDL, n = 8), and the BDL(-)/Rapa(-) group (un-treated, sham -operated control, n = 4). The BDL(+)/Rapa(+) and BDL(+)/Rapa(++) groups were administered rapamycin (2 mg/kg) for 28 d. The liver tissues were tested by immunohistochemical staining for α-smooth muscle actin (α-SMA) and cytokeratin.
The liver mRNA levels of transforming growth factor (TGF)-β1 and platelet-derived growth factor (PDGF) were measured using the polymerase chain reaction. The protein levels of liver p70s6K and p-p70s6k were determined using Western blotting. α-SMA expression was lowest in the BDL(+)/Rapa(++)group. TGF-β1 and PDGF expression levels in the rapamycin-treated group were lower than those in the un-treated group and higher than those in the control groups (TGF-β1: 0.23 ± 0.00 vs 0.34 ± 0.01, 0.23 ± 0.0 vs 0.09 ± 0.00, P < 0.0001; PDGF: 0.21 ± 0.00 vs 0.34 ± 0.01, 0.21 ± 0.0 vs 0.09 ± 0.00, P < 0.0001). The p70s6k and p-p70s6k levels decreased in the treated groups and were lowest in the BDL(+)/Rapa(++)group (p70s6k: 1.05 ± 0.17 vs 1.30 ± 0.56, 0.40 ± 0.01 vs 1.30 ± 0.56, P < 0.0001; p-p70s6k: 1.40 ± 0.5 vs 1.67 ± 0.12, 0.70 ± 0.01 vs 1.67 ± 0.12, P < 0.0001).
The results of our study indicate that rapamycin has inhibitory effects on liver fibrosis, and the treatment is most effective in the early stages of fibrosis.
研究并比较雷帕霉素在肝纤维化不同阶段的抑制作用。
对雄性Wistar大鼠（n = 24）进行胆管结扎（BDL）。将实验大鼠分为四组：BDL(+)/Rapa(-)组（未处理对照，n = 4）、BDL(+)/Rapa(+)组（BDL术后14天开始处理，n = 8）、BDL(+)/Rapa(++)组（BDL术后次日开始处理，n = 8）和BDL(-)/Rapa(-)组（未处理，假手术对照，n = 4）。BDL(+)/Rapa(+)组和BDL(+)/Rapa(++)组给予雷帕霉素（2 mg/kg），持续28天。通过免疫组织化学染色检测肝组织中α-平滑肌肌动蛋白（α-SMA）和细胞角蛋白。
采用聚合酶链反应检测肝组织中转化生长因子（TGF）-β1和血小板衍生生长因子（PDGF）的mRNA水平。采用蛋白质印迹法测定肝组织中p70s6K和p-p70s6k的蛋白水平。α-SMA表达在BDL(+)/Rapa(++)组中最低。雷帕霉素治疗组中TGF-β1和PDGF的表达水平低于未治疗组且高于对照组（TGF-β1：0.23±0.00 vs 0.34±0.01，0.23±0.0 vs 0.09±0.00，P < 0.0001；PDGF：0.21±0.00 vs 0.34±0.01，0.21±0.0 vs 0.09±0.00，P < 0.0001）。治疗组中p70s6k和p-p70s6k水平降低，且在BDL(+)/Rapa(++)组中最低（p70s6k：1.05±0.17 vs 1.30±0.56，0.40±0.01 vs 1.30±0.56，P < 0.0001；p-p70s6k：1.40±0.5 vs 1.67±0.12，0.70±0.01 vs 1.67±
