Nozato Eiji, Shiraishi Masayuki, Nishimaki Tadashi
First Department of Surgery, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
J Surg Res. 2003 Dec;115(2):226-34. doi: 10.1016/s0022-4804(03)00316-0.
The role of transforming growth factor beta (TGF-beta), a potent regulator of cellular growth, was investigated in the rat model of fulminant hepatic failure (FHF).
The rat FHF model was created by a combination of a 68% partial hepatectomy (PH) and 7% of necrosis (each n = 25 in Groups 1, 2 and 3). Adenovirus mediated gene transfer of mature human TGF-beta1 gene was performed by the systemic injection of AxCAhTGFb1 (1 x 10(9) pfu) in Group 1, 3 days before FHF. In control Groups 2 and 3, recombinant lacZ adenovirus (AxCAlacZ, Group 2) and normal saline (1 ml, Group 3) were used, instead of AxCAhTGFb1.
An excessive expression of TGF-beta1 in Group 1 resulted in an inhibition of hepatocyte proliferation (24-48 h after FHF) and gaining of liver weight (24-48 h), increased expression of HGF in liver tissue (24 h), and decreased expression of TGF-alpha (24 h), compared to those in control Groups 2 and 3. Serum IL-6 levels were also elevated by a TGF-beta1 over-expression at 24 hrs after FHF in Group 1.
The forced expression of TGF-beta1 in the FHF liver yields both a secondary increase of HGF production and a suppression of liver regeneration, which might explain the mechanism of increased serum HGF observed in a clinical FHF. TGF-beta1 is thus thought to have an important role in inhibiting liver regeneration after FHF.
在暴发性肝衰竭（FHF）大鼠模型中研究了细胞生长的强效调节因子转化生长因子β（TGF-β）的作用。
通过68%部分肝切除术（PH）和7%肝坏死相结合的方法建立大鼠FHF模型（第1、2和3组每组n = 25）。在FHF前3天，第1组通过全身注射AxCAhTGFb1（1×10⁹ pfu）进行腺病毒介导的成熟人TGF-β1基因转移。在对照组2和3中，分别使用重组lacZ腺病毒（AxCAlacZ，第2组）和生理盐水（1 ml，第3组）代替AxCAhTGFb1。
与对照组2和3相比，第1组中TGF-β1的过度表达导致肝细胞增殖受抑制（FHF后24 - 48小时）、肝脏重量增加（24 - 48小时）、肝组织中HGF表达增加（24小时）以及TGF-α表达降低（24小时）。在FHF后24小时，第1组中TGF-β1的过表达还使血清IL-6水平升高。
FHF肝脏中TGF-β1的强制表达导致HGF产生继发性增加以及肝再生受抑制，这可能解释了临床FHF中观察到的血清HGF升高的机制。因此，TGF-β1被认为在抑制FHF后的肝再生中起重要作用。
