Roles of cytokines for liver regeneration in hepatectomy rat models with postoperative infection

1：肝切除术后的肝再生和内毒素给药术后感染抑制肝切除术后的肝再生。为了阐明这种抑制作用，我们分析了肝细胞的生长速率和枯否细胞和肝细胞之间的信号，使用大鼠70%肝切除模型，有或没有内毒素（ET）的管理。在这个大鼠术后感染模型中，我们在肝切除术后第一天给予ET（1 mg/kg）。为了评估肝细胞生长率，在术后3天和7天获得的肝脏标本中进行PCNA（增殖核心核抗原）染色。PCNA阳性细胞百分比在仅肝切除的大鼠中分别为27%和17%，而在1 mg/kg ET给药的大鼠中分别为16%和10%。因此，ET给药抑制了肝切除后的肝再生。肝再生信号的分子分析采用同一肝切除模型大鼠，给予低剂量ET（30 μ g/kg）和高剂量ET（1 mg/kg）， 关于我们 方法：采用健康雄性SD大鼠，于肝切除术后3、6、12、24、48和72 h取肝组织，检测肝细胞生长因子（HGF）mRNA和c-met mRNA的表达。在仅进行肝切除的大鼠中，肝切除后12-24小时HGF表达增加，同时c-met表达增加。低剂量ET组大鼠肝细胞HGF和c-met表达水平高于对照组。高剂量ET组HGF表达高峰延迟，且与c-met表达无协同作用，提示肝切除术后给予低剂量ET可促进肝再生，而高剂量ET则抑制肝再生。ET刺激枯否细胞产生炎性细胞因子。术后严重感染引起的炎性细胞因子的过度产生可能会扰乱肝细胞生长的信号传导，导致肝再生延迟，增加模型大鼠的死亡率。少

1 : Hepatic regeneration after hepatectomy and endotoxin administrationPostoperative infection inhibits liver regeneration after hepatectomy. To elucidate this inhibition, we analyzed growth rates of hepatocyte and signals between Kupffer cells and hepatocyte using rat 70% hepatectomy model with or without endotoxin (ET) administration. In this rat postoperative infection model, we administered ET (1 mg/kg) one day after hepatectomy. To evaluate hepatocyte growth rate, PCNA (proliferative core nuclear antigen) staining was performed in liver specimens obtained at 3 and 7 postoperative days. The percentages of PCNA positive cells were 27% and 17% in the rats with only hepatectomy whereas those were 16% and 10 % in 1 mg/kg ET-administered rats, respectively. Thus, ET administration inhibited liver regeneration after hepatectomy.2. Molecular analysis for signalings of hepatic regenerationUsing the same hepatectomy model rats with low dose ET (30 mug/kg)and high dose ET (1 mg/kg)-administe … More red rats, we measured HGF (hepatocyte growth factor) mRNA and c-met mRNA expressions in the liver specimens obtained 3,6,12,24,48 and 72 hours after hepatectomy. in the rats with only hepatectomy, HGF expression increased 12-24 hours after hepatectomy and c-met expression simultaneously increased. In the low dose ET administered rats, the expression levels of HGF and c-met were higher than those in the rats without ET-administration. On the other hand, in the high dose ET administered rats, peak of HGF expression was delayed and unlikely to cooperate with c-met expression.These data suggested that low dose administration of ET after hepatectomy stimulated hepatic regeneration after hepatectomy, whereas its high dose administration inhibited. ET administration stimulated inflammatory cytokines by Kupffer cells. The overproduction of inflammatory cytokines due to postoperative severe infection might disarrange signal transduction for hepatocyte growth, which causes the delay of liver regeneration and increases the death rates of these rats model. Less