权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Recombinant Human Hepatocyte Growth Factor Protects the Liver against Hepatic Ischemia and Reperfusion Injury in Rats

重组人肝细胞生长因子保护大鼠肝脏免受缺血和再灌注损伤

基本信息

批准号：
11671195
负责人：
NAKAGAWA Manabu
金额：
$ 2.24万
依托单位：
Kansai Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

Background, Recent evidence indicates that hepatocyte growth factor (HGF) has a cytoprotective effect against hepatic injury caused by hepatotoxins and inflammatory cytokines. Studies were performed to determine whether HGF influences the survival rate of rats subjected to hepatic warm ischemia/reperfusin (WI/Rp) injury.Methods. Male Sprague-Dawley rats were subjected to toal or segmental hepatic ischemia by occluding the hepatic artery, portal vein, and bile duct with a microbascular clip. Rats were treated with four intravenous injuections of recombinant human HGF (rhHGF 1 mg/kg) or the vehicle 72, 48, 24, and 12 h before surgery.Results. None of the eight animals in the control group were alive 12 h after total hepatic WI/Rp Seven of eight animals in the rhHGF-treated group were alove more than 2 days after the reperfusion. In the model of segmental hepatic ischemia, rhHGF inhibited the increase in cytokine-induced neutrophil chemoattractant in serum. The number of neutrophils infiltrating the liver was significantly lower in the rhHGF-treated group than in the control group. rhHGF prevented increases in the activity of serum alanine transaminase and in hepatic necrosis. Experiments with proliferating cell nuclear antigen stainig demonstrated that hepatocyte proliferation markedy increased in rhHGF-treated rats as compared with controls.Conclusion. These results indicate that HGF facilitates recovery of the liver from hepatic WI/Rp injury, at least in part through the prevention of neutrophil infiltrarion and the activetion of hepatocyte proliferstion.

背景：新近研究表明，肝细胞生长因子(HGF)对肝毒素和炎性细胞因子所致的肝损伤具有细胞保护作用。研究肝细胞生长因子(HGF)对肝脏热缺血/再灌流(WI/RP)损伤大鼠存活率的影响。雄性SD大鼠采用微基底动脉夹夹闭肝动脉、门静脉和胆管造成全肝或节段性肝缺血模型。分别于手术前72、48、24、12h静脉滴注重组人肝细胞生长因子1 mg/kg或赋形剂72、48、24、12h。对照组的8只动物在全肝WI/RP后12h无一存活，而重组人肝细胞生长因子治疗组的8只动物中有7只在再灌注2天以上存活。在节段性肝缺血模型上，重组人肝细胞生长因子可抑制细胞因子诱导的中性粒细胞趋化因子的升高。重组人肝细胞生长因子治疗组大鼠肝脏中性粒细胞数明显低于对照组。重组人肝细胞生长因子可抑制血清丙氨酸转氨酶活性升高和肝组织坏死。增殖细胞核抗原染色实验显示，重组人肝细胞生长因子处理组大鼠肝细胞增殖明显高于对照组。这些结果表明，HGF促进肝脏WI/RP损伤的恢复，至少部分是通过阻止中性粒细胞的浸润和激活肝细胞的增殖来实现的。