IL-6 promotes compensatory liver regeneration in cirrhotic rat after partial hepatectomy
IL-6 promotes compensatory liver regeneration in cirrhotic rat after partial hepatectomy
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DOI：
10.1016/j.cyto.2008.03.012
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发表时间：
2008-06-01
期刊：
影响因子：
3.8
通讯作者：
Schiaffonati, Luisa
中科院分区：
文献类型：
--
作者：
Tiberio, Guido A. M.;Tiberio, Laura;Schiaffonati, Luisa
肝硬化患者的主要肝切除术与肝再生受损和衰竭相关，导致围手术期死亡率高。在这项工作中，有缺陷的再生的原因，在肝硬化和部分肝切除术在大鼠的实验模型相结合的白细胞介素-6治疗的效用进行了研究。与正常对照组相比，失代偿性肝硬化动物的存活率降低，而代偿性肝硬化动物的存活率相似，但肝DNA合成和新再生肝质量减少。缺陷性肝再生与STAT 3和NF-κ B活化的减少相关，与它们各自的抑制剂PIAS 3和Ik B α的积累增加一致，并且与Bcl-xL的诱导减少相关。重组IL-6治疗可提高失代偿性肝硬化动物的存活率，但不影响代偿性肝硬化动物的存活率，但通过恢复STAT 3和NF-κ B激活以及Bcl-xL诱导至正常对照组水平，可维持肝再生。IL-6治疗在肝硬化中发挥的促生长作用也在低的、可接受的剂量下获得。总之，我们的研究结果表明，IL-6治疗可能是治疗性的大切除术的肝硬化。(C)2008爱思唯尔有限公司保留所有权利。
Major hepatic resection in cirrhotic patients is associated with impaired liver regeneration and failure, leading to high peri-operative mortality. In this work, the causes of defective regeneration in cirrhotic liver and the utility of IL-6 treatment were investigated in an experimental model combining cirrhosis and partial hepatectomy in the rat. Relative to normal controls, decompensated cirrhotic animals showed decreased survival, while compensated cirrhotic animals showed similar survival but reduced hepatic DNA synthesis and newly regenerated liver mass amount. Defective liver regeneration was associated with a decrease in STAT3 and NF-kappa B activation, consistent with an increased accumulation of their respective inhibitors PIAS3 and IkB alpha, and with a decreased induction of Bcl-xL. Treatment with recombinant IL-6 enhanced survival of decompensated cirrhotic animals, while it did not affect survival of compensated cirrhotic animals but sustained liver regeneration, by restoring STAT3 and NF-kappa B activation and Bcl-xL induction to the levels found in normal controls. The pro-growth effects exerted by IL-6 treatment in cirrhotic liver were attained also at low, pharmacologically acceptable doses. In conclusion, our results suggest that IL-6 treatment may be therapeutic in major resection of cirrhotic liver. (C) 2008 Elsevier Ltd. All rights reserved.