Department of surgery, Laboratory of the Swiss Hepato-Pancreato-Biliary and Transplantation Center, University Hospital Zurich, Zurich, Switzerland.
Surgeon. 2012 Apr;10(2):107-13. doi: 10.1016/j.surge.2011.11.002. Epub 2011 Nov 27.
Since the discovery of the impact of serotonin in liver regeneration, this molecule has gained considerable attention in liver physio-pathology. Platelet-derived serotonin initiates liver regeneration after partial hepatectomy in various rodent models. Serotonin agonism stabilizes the hepatic microcirculation and prevents small-for-size liver graft failure. Similarly, serotonin receptor agonists improve the sinusoidal perfusion of aged liver and restore the deficient liver regeneration in old mice through a pathway dependent on vascular endothelial growth factor. Beside hepatocyte proliferation, cholangiocytes have been shown to be able to deploy serotonin as an autocrine/paracrine signal to regulate regeneration of the biliary tree. Increasing evidence indicates that serotonin is involved in many pathological conditions of the liver. For example, serotonin promotes tissue repair after ischemia/reperfusion injury. Reactive oxygen species generated by serotonin degradation contribute to steatohepatitis in rodent models. Serotonin aggravates viral hepatitis, again through vasoactive effects on the microcirculation, and plays a crucial role in the progression of hepatic fibrosis. Finally, serotonin may facilitate tumor growth of primary liver carcinoma like cholangiocarcinoma and hepatocellular carcinoma. These findings make serotonin both friend and foe for the liver. Whichever, these new data emphasize the potential of serotonin as a pharmacological target in liver disease.
自发现血清素在肝脏再生中的作用以来，这种分子在肝脏生理病理学中引起了相当大的关注。血小板衍生的血清素在各种啮齿动物模型中启动部分肝切除后的肝脏再生。血清素激动剂稳定肝微循环，防止小体积肝移植物衰竭。同样，血清素受体激动剂通过依赖血管内皮生长因子的途径改善老年肝脏的窦状隙灌注，并恢复老年小鼠中缺乏的肝脏再生。除了肝细胞增殖外，已经表明胆管细胞能够将血清素作为自分泌/旁分泌信号来调节胆管树的再生。越来越多的证据表明，血清素参与肝脏的许多病理状况。例如，血清素促进缺血/再灌注损伤后的组织修复。血清素降解产生的活性氧自由基导致啮齿动物模型中的脂肪性肝炎。血清素通过对微循环的血管活性作用加重病毒性肝炎，并在肝纤维化的进展中起关键作用。最后，血清素可能促进原发性肝癌（如胆管癌和肝细胞癌）的肿瘤生长。这些发现使血清素成为肝脏的朋友和敌人。无论如何，这些新数据强调了血清素作为肝脏疾病中一种药理学靶标的潜力。
