Immediate neuroendocrine signaling after partial hepatectomy through acute portal hyperpressure and cholestasis
Immediate neuroendocrine signaling after partial hepatectomy through acute portal hyperpressure and cholestasis
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DOI：
10.1016/j.jhep.2010.07.012
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发表时间：
2011-03-01
影响因子：
25.7
通讯作者：
Tordjmann, Thierry
中科院分区：
文献类型：
--
作者：
Doignon, Isabelle;Julien, Boris;Tordjmann, Thierry
背景与目的：肝部分切除术后早期神经内分泌通路参与肝再生。我们研究了这些途径之一，涉及急性胆汁淤积，立即门静脉高压，精氨酸加压素（AVP）secrety.Methods：手术程序（PH，门静脉狭窄（PVS），胆管结扎（BDL），脊髓损伤（SCL））和治疗（辣椒素，胆汁酸（BA），油酸（OA））进行大鼠和/或野生型或TGR 5（GPBAR 1）基因敲除小鼠。在这些模型中，分析AVP分泌视上核（SON）的激活，以及血浆BA、AVP和门静脉压（PVP）。结果：急性胆汁淤积（模拟BDL或BA注射）和门静脉高压（模拟PVS）可独立激活SON和AVP分泌。PH或BDL后BA在脑内蓄积，TGR 5在SON表达。SON活化由TGR 5激动剂OA模拟，并在BDL后在TGR 5 KO小鼠中被抑制。一个传入神经通路也有助于后PH AVP分泌，辣椒素治疗或SCL导致较弱的SON激活后PH。结论：在啮齿动物PH后，急性胆汁淤积和门静脉高压症，通过神经和内分泌途径，刺激AVP的分泌，可能保护肝脏免受剪切应力和胆汁酸超载。活体捐赠者的数据表明，这一途径也可能在人类中发挥作用。(C)2010年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background & Aims: Early neuroendocrine pathways contribute to liver regeneration after partial hepatectomy (PH). We investigated one of these pathways involving acute cholestasis, immediate portal hyperpressure, and arginine vasopressin (AVP) secretion.Methods: Surgical procedure (PH, Portal vein stenosis (PVS), bile duct ligation (BDL), spinal cord lesion (SCL)) and treatments (capsaicin, bile acids (BA), oleanolic acid (OA)) were performed on rats and/or wild type or TGR5 (GPBAR1) knock-out mice. In these models, the activation of AVP-secreting supraoptic nuclei (SON) was analyzed, as well as plasma BA, AVP, and portal vein pressure (PVP). Plasma BA, AVP, and PVP were also determined in human living donors for liver transplantation.Results: Acute cholestasis (mimicked by BDL or BA injection) as well as portal hyperpressure (mimicked by PVS) independently activated SON and AVP secretion. BA accumulated in the brain after PH or BDL, and TGR5 was expressed in SON. SON activation was mimicked by the TGR5 agonist OA and inhibited in TGR5 KO mice after BDL. An afferent nerve pathway also contributed to post-PH AVP secretion, as capsaicin treatment or SCL resulted in a weaker SON activation after PH.Conclusions: After PH in rodents, acute cholestasis and portal hypertension, via the nervous and endocrine routes, stimulate the secretion of AVP that may protect the liver against shear stress and bile acids overload. Data in living donors suggest that this pathway may also operate in humans. (C) 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.