Autonomic Regulation of Liver Regeneration After Partial Hepatectomy in Mice
Autonomic Regulation of Liver Regeneration After Partial Hepatectomy in Mice
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DOI：
10.1016/j.jss.2008.02.059
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发表时间：
2009-04-01
影响因子：
2.2
通讯作者：
Ohkohchi, Nobuhiro
中科院分区：
文献类型：
--
作者：
Ikeda, Osamu;Ozaki, Michitaka;Ohkohchi, Nobuhiro
背景/目标。迷走神经自主神经被认为在肝脏再生中起重要作用，因为肝脏迷走神经切断延迟了肝脏DNA的合成。然而，副交感迷走神经如何参与肝脏再生仍不清楚。Kupffer细胞位于邻近肝细胞的肝窦内，可能通过释放白细胞介素6(IL-6)来调节肝再生。本研究探讨了迷走神经的作用以及Kupffer细胞如何参与副交感神经介导的小鼠肝脏再生。我们进行了肝分支迷走神经切断手术，然后进行肝部分切除(PH)；一些小鼠在PH前接受了乙酰胆碱(ACh)激动剂/拮抗剂。然后我们评估肝脏再生和信号转导和转录激活子-3(STAT3)的激活。我们还研究了ACh是否刺激Kupffer细胞释放IL-6。外科迷走神经切断术损害了肝脏再生。在肝切除后被IL-6激活的STAT3在肝再生中起关键作用，而在去迷走神经的小鼠肝切除后STAT3的激活较少。给予去迷走神经的小鼠注射ACh激动剂，可恢复PH后STAT3的激活。此外，ACh还可促进体外培养的Kupffer细胞释放IL-6。副交感神经系统(迷走神经)通过刺激Kupffer细胞释放IL-6，继而激活肝细胞中的STAT3，促进肝切除后的肝再生。(C)2009 Elsevier Inc.保留所有权利。
Background/Aims. The autonomic vagus nerve is thought to play an essential role in liver regeneration since hepatic vagotomy delays hepatic DNA synthesis. However, how the parasympathetic vagus nerve is involved in liver regeneration remains obscure. Kupffer cells are located in liver sinusoids adjacent to hepatocytes and might regulate liver regeneration by releasing interleukin-6 (IL-6). The present study examines the role of the vagus nerve and how Kupffer cells are involved in parasympathetic nerve-mediated liver regeneration in mice.Methods. We performed surgical vagotomy of the hepatic branch and then partial hepatectomy (PH); some mice received acetylcholine (ACh) agonist/antagonist before PH. We then evaluated liver regeneration and signal transducer and activator of transcription-3 (STAT3) activation. We also investigated whether ACh stimulates IL-6 release from Kupffer cells.Results. Surgical vagotomy impaired liver regeneration. STAT3, which is activated by IL-6 after hepatectomy and plays a pivotal role in liver regeneration, was less activated in vagotomized mice after PH. Post-PH STAT3 activation was recovered by administering vagotomized mice with an ACh agonist. Furthermore, ACh stimulated IL-6 release in Kupffer cells in vitro.Conclusion. The parasympathetic system (vagus nerve) contributes to liver regeneration after hepatectomy by stimulating IL-6 release from Kupffer cells followed by STAT3 activation in hepatocytes. (C) 2009 Elsevier Inc. All rights reserved.