Attenuation of N-nitrosodiethylamine-induced liver fibrosis by high-molecular-weight fucoidan derived from Cladosiphon okamuranus
Attenuation of N-nitrosodiethylamine-induced liver fibrosis by high-molecular-weight fucoidan derived from Cladosiphon okamuranus
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DOI：
10.1111/j.1440-1746.2009.06187.x
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发表时间：
2010-10-01
影响因子：
4.1
通讯作者：
Nagamine, Takeaki
中科院分区：
文献类型：
--
作者：
Nakazato, Kyoumi;Takada, Hisashi;Nagamine, Takeaki
背景与目的：肝纤维化与多种慢性肝病的进展密切相关。岩藻依聚糖硫酸酯具有抗炎、抗氧化、抗纤维化等多种生物学活性。本研究的目的是确定是否口服褐藻糖胶管理抑制N-亚硝基二乙胺（DEN）诱导的肝纤维化。方法：肝纤维化大鼠注射DEN（50 mg/kg）。大鼠被给予2%的粗岩藻聚糖溶液或2%的高分子量（HMW）岩藻聚糖溶液。结果：DEN + HMW褐藻糖胶组大鼠肝纤维化程度和肝羟脯氨酸含量均明显低于DEN组，DEN + HMW褐藻糖胶组大鼠肝纤维化程度明显低于DEN组，DEN + HMW褐藻糖胶组大鼠肝羟脯氨酸含量明显低于DEN组。在DEN+粗岩藻依聚糖组中，抗纤维形成不显著。DEN可显著增加肝脏信使RNA水平和转化生长因子β 1免疫组化染色。这种增加被HMW岩藻依聚糖减弱。DEN可增加肝脏趋化因子配体12的表达。这种增加被HMW岩藻依聚糖抑制。HMW褐藻糖胶显著降低DEN诱导的丙二醛水平。此外，褐藻糖胶显着增加金属硫蛋白在肝脏中的表达。岩藻多糖在肝组织中的免疫组化染色结果表明，岩藻多糖能明显抑制DEN诱导的肝硬化大鼠肝纤维化的发生，而在粗岩藻多糖处理的大鼠肝组织中，岩藻多糖的免疫组化染色结果表明，岩藻多糖能通过下调转化生长因子β 1和趋化因子配体12的表达而抑制DEN诱导的肝硬化大鼠肝纤维化的发生。
Background and Aim:Liver fibrosis is closely associated with the progression of various chronic liver diseases. Fucoidan exhibits different biological properties such as anti-inflammatory, anti-oxidant and anti-fibrotic activities. The aim of this study was to determine whether oral fucoidan administration inhibits N-nitrosodiethylamine (DEN)-induced liver fibrosis.Methods:Liver fibrosis was induced in rats by injecting DEN (50 mg/kg). Rats were given 2% of crude fucoidan solution or 2% of high-molecular-weight (HMW) fucoidan solution. They were divided into a crude fucoidan group, an HMW fucoidan group, a DEN alone group, a DEN + crude fucoidan group, a DEN + HMW fucoidan group and a control group.Results:Liver fibrosis and hepatic hydroxyproline levels were significantly more decreased in the DEN + HMW fucoidan group than in the DEN-alone group. Anti-fibrogenesis was unremarkable in the DEN + crude fucoidan group. Hepatic messenger RNA levels and immunohistochemistry of transforming growth factor beta 1 were markedly increased by DEN. This increase was attenuated by HMW fucoidan. Hepatic chemokine ligand 12 expression was increased by DEN. This increase was suppressed by HMW fucoidan. HMW fucoidan significantly decreased the DEN-induced malondialdehyde levels. Also, fucoidan markedly increased metallothionein expression in the liver. Fucoidan was clearly observed in the liver by immunohistochemical staining in HMW fucoidan-treated rats, while it was faintly stained in the livers of crude fucoidan-treated rats.Conclusion:These findings suggest that the HMW fucoidan treatment causes anti-fibrogenesis in DEN-induced liver cirrhosis through the downregulation of transforming growth factor beta 1 and chemokine ligand 12 expressions, and that scavenging lipid peroxidation is well-incorporated in the liver.