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

1：肝切除术后肝脏再生与内毒素给药术后感染抑制肝切除术后肝脏再生。为了阐明这种抑制作用，我们使用有或没有内毒素（ET）给药的70%大鼠肝切除术模型，分析了肝细胞的生长速度和Kupffer细胞与肝细胞之间的信号。在大鼠术后感染模型中，我们在肝切除术后1天给予ET （1 mg/kg）。为了评估肝细胞的生长速度，在术后3天和7天对肝标本进行PCNA（增殖核心核抗原）染色。仅肝切除术大鼠的PCNA阳性细胞百分比为27%和17%，而给予1 mg/kg et大鼠的PCNA阳性细胞百分比分别为16%和10%。因此，ET抑制肝切除术后肝脏再生。采用相同的肝切除模型大鼠，分别给予低剂量ET （30 mg/kg）和高剂量ET (1 mg/kg)，在肝切除后3、6、12、24、48和72 h的肝脏标本中检测肝细胞生长因子mRNA和c-met mRNA的表达。仅行肝切除术的大鼠，肝切除术后12-24小时HGF表达升高，c-met表达同时升高。低剂量ET大鼠HGF和c-met的表达水平高于未给ET大鼠。另一方面，在高剂量ET给药大鼠中，HGF表达峰值延迟，不太可能与c-met表达协同。这些数据表明，肝切除术后低剂量给药ET刺激肝切除术后肝再生，而高剂量给药则抑制肝切除术后肝再生。ET通过Kupffer细胞刺激炎症细胞因子。术后严重感染导致炎性细胞因子过量产生，可能扰乱肝细胞生长的信号转导，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