ANTIBODIES TO TUMOR-NECROSIS-FACTOR-ALPHA INHIBIT LIVER-REGENERATION AFTER PARTIAL-HEPATECTOMY
ANTIBODIES TO TUMOR-NECROSIS-FACTOR-ALPHA INHIBIT LIVER-REGENERATION AFTER PARTIAL-HEPATECTOMY
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DOI：
10.1152/ajpgi.1992.263.4.g579
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发表时间：
1992-10-01
影响因子：
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通讯作者：
DIEHL, AM
中科院分区：
文献类型：
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作者：
AKERMAN, P;COTE, P;DIEHL, AM
肝脏中产生的某些细胞因子可能作为生长因子促进伤口愈合，因此可能影响肝脏再生。然而，这一假设尚未得到直接验证。为了确定部分肝切除术（PH）引起的细胞因子反应是否调节肝脏再生过程，在PH前1小时，向成年雄性大鼠腹腔注射山羊抗大鼠肿瘤坏死因子多克隆抗体（TNF； 15马克杯/克体wt）或等量的山羊抗大鼠免疫球蛋白g。动物在PH后12、24、48或72小时，注射[h -3]胸腺嘧啶1小时后死亡。采用L929细胞毒性法测定血清TNF水平，采用酶联免疫吸附法测定血清TNF抗体滴度，采用B9细胞生物测定法测定血清白细胞介素-6 （IL-6）浓度。通过[H-3]胸苷并入肝脏DNA和增殖细胞核抗原（PCNA）表达的免疫组织化学证据来评估肝脏再生。在治疗大鼠中检测到TNF抗体，而在对照组中未检测到。12 h时滴度最高，随后逐渐下降。虽然血清中未检测到TNF，但ph前抗TNF治疗可显著抑制ph后血清IL-6浓度的升高。抗tnf预处理还抑制[H-3]胸腺嘧啶并入DNA，以及肝细胞和肝非实质细胞PCNA的表达。这些数据表明TNF正调节PH后肝脏再生。
Certain cytokines that are produced in liver may act as growth factors to facilitate wound healing and, hence, may influence liver regeneration. However, this hypothesis has not been directly tested. To determine whether the cytokine response evoked by partial hepatectomy (PH) modulates the process of liver regeneration, adult male rats were injected intraperitoneally with either goat polyclonal antibodies to rat tumor necrosis factor (TNF; 15 mug/g body wt) or an equal amount of goat anti-rat immunoglobulin G 1 h before PH. Animals were killed at 12, 24, 48, or 72 h post-PH, 1 h after injection with [H-3]thymidine. Serum TNF levels were measured with the L929 cytotoxicity assay, titers of antibody to TNF were determined by enzyme-linked immunoabsorbent assay, and interleukin-6 (IL-6) concentrations were measured by B9 cell bioassay. Liver regeneration was assessed by [H-3]thymidine incorporation into hepatic DNA and by immunohistochemical evidence of proliferating cell nuclear antigen (PCNA) expression. Antibodies to TNF were detected in treated rats but not in controls. Titers were highest at 12 h and progressively fell. Although TNF was never detected in serum, treatment with anti-TNF pre-PH significantly inhibited increases in serum IL-6 concentration post-PH. Anti-TNF pretreatment also inhibited [H-3]thymidine incorporation into DNA, as well as expression of PCNA by both hepatocytes and liver nonparenchymal cells. These data indicate that TNF positively modulates liver regeneration after PH.