Sakaida I, Matsumura Y, Akiyama S, Hayashi K, Ishige A, Okita K
First Department of Internal Medicine, School of Medicine, Yamaguchi University, Japan.
J Hepatol. 1998 Feb;28(2):298-306. doi: 10.1016/0168-8278(88)80017-5.
BACKGROUND/AIM: A herbal medicine, Sho-saiko-to (TJ-9), has recently been orally administered to patients with chronic liver disease in Japan and has been reported to inhibit the development of hepatocellular carcinoma. The aim of this study was to investigate whether TJ-9 has an inhibitory effect on the development of preneoplastic lesions and liver fibrosis in rats.
The effects of the TJ-9 were examined using the choline-deficient L-amino acid-defined (CDAA) diet-induced liver fibrosis model in 16-week-old male Wistar rats.
TJ-9 (1% w/w) prevented fibrosis, as indicated by reduced hydroxyproline content in the liver and inhibition of the increase in a serum marker of fibrosis (hyaluronic acid), without reducing the increase in serum alanine aminotransferase and aspartate aminotransferase. TJ-9 also reduced the expression of type III procollagen alpha 1 mRNA in the liver, as well as the proliferation of myofibroblast-like cells (activated stellate cells, activated Ito cells). Furthermore, TJ-9 reduced the number of preneoplastic lesions, detected as enzyme-altered (glutathione S-transferase placental form-positive) lesions, in the liver.
These results indicate that the herbal medicine Sho-saiko-to (TJ-9) prevents fibrosis as well as preneoplastic lesions, not by inhibiting hepatocyte cell death but by inhibiting the activation of stellate cells, which are considered to be the main collagen-producing cells, leading to a reduction in the development of preneoplastic lesions.
背景/目的：一种草药制剂小柴胡汤（TJ - 9）最近在日本已被口服用于慢性肝病患者，并且有报道称其可抑制肝细胞癌的发生。本研究的目的是调查TJ - 9对大鼠癌前病变和肝纤维化的发展是否具有抑制作用。
在16周龄雄性Wistar大鼠中，使用胆碱缺乏的L - 氨基酸限定（CDAA）饮食诱导的肝纤维化模型来检测TJ - 9的作用。
TJ - 9（1% w/w）可预防纤维化，表现为肝脏中羟脯氨酸含量降低以及血清纤维化标志物（透明质酸）升高受到抑制，同时血清丙氨酸氨基转移酶和天冬氨酸氨基转移酶升高未受影响。TJ - 9还降低了肝脏中III型前胶原α1 mRNA的表达以及肌成纤维细胞样细胞（活化星状细胞、活化伊托细胞）的增殖。此外，TJ - 9减少了肝脏中作为酶改变（谷胱甘肽S - 转移酶胎盘型阳性）病变检测到的癌前病变数量。
这些结果表明，草药制剂小柴胡汤（TJ - 9）可预防纤维化以及癌前病变，其机制不是通过抑制肝细胞死亡，而是通过抑制被认为是主要胶原产生细胞的星状细胞的活化，从而减少癌前病变的发展。
