Continuos intravenous infusion of atrial natriuretic peptide(ANP) prevented liver fibrosis in rat

Continuos intravenous infusion of atrial natriuretic peptide(ANP) prevented liver fibrosis in rat
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DOI:
10.1016/j.bbrc.2008.10.154
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发表时间:
2009-01-16
影响因子:
3.1
通讯作者:
Sakaida, Isao
Sakaida, Isao
中科院分区:
生物学4区
文献类型:
--
作者:
Ishigaki, Noriko;Yamamoto, Naold;Sakaida, Isao

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心房钠尿肽(ANP)在临床上被用作治疗急性心力衰竭的药物,近年来有报道其抑制心、肺纤维化的作用。本研究旨在探讨心钠素对肝纤维化的抑制作用。在体外,用ANP处理大鼠肝星状细胞系(HSC-T6)。在体内,Wister大鼠经腹腔注射二甲基亚硝胺(DMN),每周两次,持续4周。ANP组于DMN给药1周后,用24 h持续静脉泵给药3周。在体外实验中,ANP可抑制HSC的α-SMA表达,抑制HSC的生长,降低1型前胶原和TIMP-1、-2的表达。在体内实验中,ANP组血清AST、ALT、HA水平明显降低。ANP可抑制肝纤维化。ANP还可降低Ⅰ型前胶原、TIMP-1、TIMP-2和α-SMA、TGF-β 1的基因表达。结果表明,持续输注ANP具有特异性抑制HSC活化和保护肝细胞的作用,并有抑制肝纤维化的作用。(C)2008年由Elsevier Inc.出版
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 24 h 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-beta 1 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. (C) 2008 Published by Elsevier Inc.