Continuos intravenous infusion of atrial natriuretic peptide (ANP) prevented liver fibrosis in rat.
The atrial natriuretic peptide (ANP) are used as the acute heart failure treatment in clinical and reported the suppression of fibrosis in the heart, lung recently. The aim of this study was to analyze the suppressive effect of liver fibrosis about ANP. In vitro, rat hepatic stellate cell line (HSC-T6) were treated with ANP. In vivo, Wister rats were injected with dimethylnitrosamine (DMN) twice a week via intra-peritoneal for 4 weeks. ANP group was given by continuance intravenous dosage system used 24h infusion pump for 3 weeks after 1 week of DMN administration. In vitro, ANP suppressed alpha-SMA expression and was inhibited the growth of HSC, and reduced the expression of type 1 procollagen, TIMP-1, -2 expression. In vivo, The ANP group showed lower serum AST, ALT, HA level. Liver fibrosis was suppressed by ANP. ANP also decreased gene expression of type 1 procollagen, TIMP-1, -2 and alpha-SMA, TGF-beta1 expression. Our results showed that continuous ANP infusion has the specific capacity of inhibiting HSC activation and protecting hepatocytes and the useful capacity to suppress the liver fibrosis.
Ishigaki
Noriko
N
Department of Gastroenterology and Hepatology, Yamaguchi University, Graduated School of Medicine, Minami-Kogushi 1-1-1 Ube, Yamaguchi 755-8505, Japan.
Yamamoto
Naoki
N
Jin
Haiyan
H
Uchida
Kouichi
K
Terai
Shuji
S
Sakaida
Isao
I
D000199:Actins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage*; D002460:Cell Line; D004128:Dimethylnitrosamine / Q000633:toxicity; D015870:Gene Expression; D007262:Infusions, Intravenous; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D011347:Procollagen / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis
D000199:Actins; D009320:Atrial Natriuretic Factor; D004128:Dimethylnitrosamine; D011347:Procollagen; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D053773:Transforming Growth Factor beta1; C498862:Acta2 protein, rat