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

1：肝切除术后肝再生及内毒素应用术后感染抑制肝切除术后肝再生。为了阐明这种抑制作用，我们在大鼠70%肝切除模型上分析了肝细胞的生长速度以及枯否细胞与肝细胞之间的信号传递。在这个大鼠术后感染模型中，我们在肝切除后一天给予ET(1 mg/kg)。分别于术后第3天和第7天取肝组织标本进行增殖细胞核抗原(增殖细胞核抗原)染色，以评价肝细胞生长率。单纯肝切除组增殖细胞核抗原阳性细胞百分率分别为27%和17%，1 mg/kg组分别为16%和10%。因此，ET可抑制肝切除后的肝再生。大剂量ET(1 mg/kg)和低剂量ET(30 mg/kg)联合应用…对肝切除大鼠肝再生信号分子分析分别于肝切除后3、6、12、24、48、72小时取肝组织，检测肝细胞生长因子(HGF)和c-met基因的表达。单纯肝切除大鼠，肝切除后12~24小时HGF表达增加，c-met表达增加。低剂量ET组大鼠肝细胞生长因子和c-Met的表达水平均高于未用药组。另一方面，大剂量ET组大鼠肝细胞生长因子表达高峰延迟，与c-met表达不相协调，提示肝切除后给予低剂量ET可促进肝切除后肝再生，而大剂量ET可抑制肝切除后肝再生。ET可通过库普弗细胞刺激炎症细胞因子的产生。术后严重感染所致的炎性细胞因子产生过多，可能导致肝细胞生长信号转导紊乱，导致肝再生延迟，增加模型大鼠的死亡率。较少

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