Kon Kazuyoshi, Ikejima Kenichi, Hirose Miyoko, Yoshikawa Mutsuko, Enomoto Nobuyuki, Kitamura Tsuneo, Takei Yoshiyuki, Sato Nobuhiro
Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
Biochem Biophys Res Commun. 2002 Feb 15;291(1):55-61. doi: 10.1006/bbrc.2002.6385.
Here we investigated the effect of pioglitazone, a peroxisome proliferator-activated receptor (PPAR)-gamma ligand, on early-phase hepatic fibrogenesis in vivo caused by acute carbon tetrachloride (CCl(4)) administration in the rat. Pioglitazone (1 mg/kg BW) prevented pericentral fibrosis and induction of alpha-smooth muscle actin (SMA) 72 h after CCl(4) administration (1 ml/kg BW). CCl(4) induction of alpha1(I)procollagen mRNA in the liver was blunted by pioglitazone to the levels almost 2/3 of CCl(4) alone. Pioglitazone also prevented CCl(4)-induced hepatic inflammation and necrosis, as well as increases in serum tumor necrosis factor-alpha levels. Further, pioglitazone inhibited the induction of alphaSMA and type I collagen in primary cultured hepatic stellate cells in a dose-dependent manner. In conclusion, pioglitazone inhibits both hepatic inflammation and activation of hepatic stellate cells, thereby ameliorating early-phase fibrogenesis in the liver following acute CCl(4).
在此，我们研究了吡格列酮（一种过氧化物酶体增殖物激活受体（PPAR）-γ配体）对大鼠急性给予四氯化碳（CCl₄）所致体内早期肝纤维化的影响。吡格列酮（1毫克/千克体重）可预防CCl₄（1毫升/千克体重）给药72小时后中央静脉周围纤维化及α平滑肌肌动蛋白（SMA）的诱导。吡格列酮使肝脏中α1（I）前胶原mRNA的CCl₄诱导作用减弱至仅CCl₄作用时水平的近2/3。吡格列酮还可预防CCl₄诱导的肝脏炎症和坏死，以及血清肿瘤坏死因子-α水平的升高。此外，吡格列酮以剂量依赖的方式抑制原代培养肝星状细胞中αSMA和I型胶原的诱导。总之，吡格列酮可抑制肝脏炎症和肝星状细胞的激活，从而改善急性CCl₄后肝脏的早期纤维化。
