Reduction of fibrosis in a rat model of non-alcoholic steatohepatitis cirrhosis by human HGF gene transfection using electroporation.
OBJECTIVE
To study the histological changes caused by transfection of the hepatocyte growth factor (HGF) gene using electroporation (EP) in a non-alcoholic steatohepatitis (NASH) cirrhotic liver model.


METHODS
NASH cirrhotic livers were prepared by administering a choline-deficient diet to 5-week-old male Wister rats for 12 weeks. Three groups of rats were used: rats in the G(+) group were transfected with the GFP gene using EP, rats in the H(+) group were transfected with the HGF gene using EP, and rats in the H(-) group were only injected with the HGF gene. Rats were sacrificed 2 days after gene transfection, and the Azan positive rate (APR) and Sudan positive rate (SPR) were calculated to evaluate fibrosis and fatty changes.


RESULTS
The APR of the NASH cirrhotic livers was significantly higher than that in the normal livers. The APR did not decrease in the G(+) group and the H(-) group, but decreased significantly in the nonelectroporated as well as electroporated areas of the H(+) group. For SPR, there were no significant differences between the G(+), H(-), and H(+) groups.


CONCLUSIONS
The improvement of fibrosis was not significant when a direct injection of the HGF gene was used alone, but it was enhanced by the concomitant use of EP. However, no efficacy was observed in fat components. These findings suggest that transfection of the HGF gene by EP may lead to an improvement of irreversible cirrhotic livers to reversible fatty livers.
Kiyama
Shigeru
S
Department of Advanced Surgery, Gifu University Graduate School of Medicine, Gifu, Japan. s-kiyama@gifu-u.ac.jp
Yamada
Takuya
T
Iwata
Hisashi
H
Sekino
Takafumi
T
Matsuo
Hiroshi
H
Yoshida
Naomasa
N
Miyahara
Toshiyuki
T
Umeda
Yukio
Y
Matsuno
Yukihiro
Y
Kimura
Masaki
M
Matsumoto
Kunio
K
Nakamura
Toshikazu
T
Takemura
Hirofumi
H
D000818:Animals; D004195:Disease Models, Animal; D018274:Electroporation; D005234:Fatty Liver / Q000150:complications*; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology / Q000235:genetics / Q000628:therapy*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014162:Transfection
C066855:HGF protein, human; D017228:Hepatocyte Growth Factor