Kupffer cells modulate splenic, interleukin-10 production in endotoxin-induced liver injury after partial hepatectomy.

部分肝切除术后内毒素诱导的肝损伤中，库普弗细胞调节脾脏、白细胞介素 10 的产生。

• 批准号: 12671218
• 负责人: NAKAMURA Toshio
• 金额: $ 1.73万
• 依托单位: Hamamatsu University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671218/
• 关键词: hepatectomy; cytokine; il-10; tnf; endotoxin; lps; Kupffer cell; gadolinium chloride; GdCl_3; Kupffer細胞; Gadolinium chloride; 脾臓; 抗炎症性サイトカイン

Background : This study was conducted to investigate the implication of Kupffer cells and the spleen in interleukin (IL)-10 production in endotoxin-induced liver injury after hepatectomy.Materials and Methods : Rats were divided into five groups : the S group, sham-operation ; the SG group, sham-operation followed by intravenous gadolinium chloride (GdCl3 : 7mg/kg) administration to inhibit Kupffer cell function ; the H group, two-thirds hepatectomy ; the HG group, hepatectomy and subsequent GdCl3 administration ; the HGS group, hepatectomy and splenectomy with GdCl3 administration.Lipopolysaccharide (1.5mg/kg) was intravenously administered for each group 48 hours after surgery. Results : GdCl3 treatment significantly suppressed the elevation of plasma alanine aminotransferase and tumor necrosis factor (TNF)-a by lipopolysaccharide administration, and completely inhibited the induction of hepatic tissue TNF-a and IL-10 mRNAs. In the HG group, plasma IL-10 levels were significantly higher than those in the H and HGS groups and splenic IL-10 mRNA was markedly enhanced 1 hour after lipopolysaccharide administration. Plasma TNF-a /IL-10 ratio was higher in the rank order H>HGS>HG. The 24-hour mortality (H group, 67% ; HGS group, 33% ; HG group, 20%) and hepatic parenchymal damage was in the same order. Conclusion : Kupffer cells after hepatectomy may aggravate endotoxin-induced liver injury via down-regulation of IL-10 production in the spleen.

背景：本研究旨在探讨Kupffer细胞和脾脏在内毒素诱导的肝切除术后肝损伤中白细胞介素(IL)-10产生中的作用。材料与方法：将大鼠分为5组：S组，假手术组；SG组假手术后静脉注射氯化钆（GdCl3: 7mg/kg）抑制库普弗细胞功能；H组，三分之二肝切除术；HG组，肝切除术和随后给药GdCl3；HGS组，肝脾切除加GdCl3。各组术后48小时静脉给予脂多糖1.5mg/kg。结果：GdCl3可显著抑制脂多糖给药对血浆丙氨酸转氨酶和肿瘤坏死因子(TNF)-a的升高，完全抑制肝组织TNF-a和IL-10 mrna的诱导。HG组大鼠血浆IL-10水平显著高于H组和HGS组，且脂多糖给药1 H后脾IL-10 mRNA水平显著升高。血浆TNF-a /IL-10比值在h> HGS >hg等级中较高。24小时死亡率（H组67%，HGS组33%，HG组20%）和肝实质损害程度排序相同。结论：肝切除术后Kupffer细胞可能通过下调脾脏IL-10的产生而加重内毒素所致的肝损伤。