Low molecular weight heparin prevents hepatic fibrogenesis caused by carbon tetrachloride in the rat
Low molecular weight heparin prevents hepatic fibrogenesis caused by carbon tetrachloride in the rat
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DOI：
10.1016/j.jhep.2006.08.023
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发表时间：
2007-02-01
影响因子：
25.7
通讯作者：
Sato, Nobuhiro
中科院分区：
文献类型：
--
作者：
Abe, Wataru;Ikejima, Kenichi;Sato, Nobuhiro
背景/目标：在这项研究中，我们研究了达肝素钠，一种低分子量（LMW）肝素，对慢性四氯化碳（CCl 4）给药引起的大鼠肝纤维化的影响。方法：雌性Wistar大鼠单次或重复腹腔注射CCl 4（1 ml/kg，每周两次）和达肝素结果：达肝素不能预防急性CCl 4诱导的肝坏死和血清转氨酶水平升高;然而，增殖细胞核抗原（PCNA）阳性肝细胞显着增加后24小时，同时给予四氯化碳和达肝素。有趣的是，当同时给予达肝素时，注射CCl 4后12 h血清肝细胞生长因子（HGF）水平几乎加倍。每日联合使用达肝素可显著改善7周CCl 4治疗后的肝纤维化。事实上，达肝素在很大程度上抑制了肝脏中CCl 4诱导的平滑肌α-肌动蛋白表达、α 1（I）前胶原和转化生长因子（TGF）-β 1 mRNA水平。此外，达肝素钝化血小板衍生生长因子（PDGF）诱导的增加5-溴-2 '脱氧尿苷（BrdU）的摄取在3天培养的肝星状细胞（HSCs）在剂量依赖mathematics.Conclusions：达肝素增强肝再生和最大限度地减少慢性四氯化碳治疗引起的肝纤维化。这些作用的潜在机制很可能涉及HGF的上调和HSC增殖的抑制。(c)2006年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background/Aims: In this study, we investigated the effect of dalteparin sodium, a low molecular weight (LMW)-heparin, on hepatic fibrogenesis caused by chronic carbon tetrachloride (CCl4) administration in the rat.Methods: Female Wistar rats were given a single, or repeated intraperitoneal injections of CCl4 (1 ml/kg, twice per week) and dalteparin (50 IU/kg, daily) for 7 weeks.Results: Dalteparin did not prevent acute CCl4-induced hepatic necrosis and elevation in serum aminotransferases levels; however, proliferating cell nuclear antigen (PCNA)-positive hepatocytes were dramatically increased 24 h after simultaneous administration of CCl4 and dalteparin. Interestingly, serum hepatocyte growth factor (HGF) levels 12 h after injection of CCl4 were almost doubled when dalteparin was given simultaneously. Hepatic fibrosis following 7-week CCl4 treatment was markedly ameliorated by daily co-administration of dalteparin. Indeed, dalteparin largely inhibited CCl4-induction of smooth muscle a-actin expression, alpha 1(I)procollagen and transforming growth factor (TGF)-beta 1 mRNA levels in the liver. Further, dalteparin blunted platelet-derived growth factor (PDGF)-induced increases in 5-bromo-2' deoxyuridine (BrdU) uptake in 3-day cultured hepatic stellate cells (HSCs) in a dose-dependent manner.Conclusions: Dalteparin enhances hepatic regeneration and minimizes hepatic fibrogenesis caused by chronic CCl4 treatment. The mechanism underlying these effects most likely involves both up-regulation of HGF and inhibition of HSC proliferation. (c) 2006 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.