Sakakura Y, Kaibori M, Oda M, Okumura T, Kwon A H, Kamiyama Y
First Department of Surgery, Department of Medical Chemistry, Kansai Medical University, 10-15 Fumizonocho, Moriguchi, Osaka, 570-8507, Japan.
J Surg Res. 2000 Aug;92(2):261-6. doi: 10.1006/jsre.2000.5913.
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/reperfusion (WI/Rp) injury.
Male Sprague-Dawley rats were subjected to total or segmental hepatic ischemia by occluding the hepatic artery, portal vein, and bile duct with a microvascular clip. Rats were treated with four intravenous injections of recombinant human HGF (rhHGF 1 mg/kg) or the vehicle 72, 48, 24, and 12 h before surgery.
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 alive 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 staining demonstrated that hepatocyte proliferation markedly increased in rhHGF-treated rats as compared with controls.
These results indicate that HGF facilitates recovery of the liver from hepatic WI/Rp injury, at least in part through the prevention of neutrophil infiltration and the activation of hepatocyte proliferation.
最近有证据表明，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。本研究旨在确定HGF是否影响肝热缺血/再灌注（WI/Rp）损伤大鼠的存活率。
采用微血管夹夹闭肝动脉、门静脉和胆管，对雄性Sprague-Dawley大鼠进行全肝或部分肝缺血处理。在手术前72、48、24和12小时，对大鼠进行四次重组人HGF（rhHGF 1mg/kg）或赋形剂的静脉注射。
全肝WI/Rp术后12小时，对照组的8只动物均死亡。rhHGF治疗组的8只动物中有7只在再灌注后存活超过2天。在部分肝缺血模型中，rhHGF抑制血清中细胞因子诱导的中性粒细胞趋化因子的增加。rhHGF治疗组肝脏中浸润的中性粒细胞数量明显低于对照组。rhHGF可防止血清丙氨酸转氨酶活性升高和肝坏死。增殖细胞核抗原染色实验表明，与对照组相比，rhHGF治疗组大鼠的肝细胞增殖明显增加。
这些结果表明，HGF至少部分通过防止中性粒细胞浸润和激活肝细胞增殖，促进肝脏从肝WI/Rp损伤中恢复。
