INSERM U.757, Université Paris Sud, bât. 443, 91405 Orsay, France.
J Hepatol. 2011 Mar;54(3):481-8. doi: 10.1016/j.jhep.2010.07.012. Epub 2010 Sep 22.
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.
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.
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.
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.
部分肝切除术（PH）后早期的神经内分泌途径有助于肝再生。我们研究了涉及急性胆汁淤积、即刻门静脉高压和精氨酸加压素（AVP）分泌的途径之一。
对大鼠和/或野生型或 TGR5（GPBAR1）敲除小鼠进行手术（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）、齐墩果酸（OA））。在这些模型中，分析了 AVP 分泌的视上核（SON）的激活情况，以及血浆 BA、AVP 和门静脉压（PVP）。还在进行肝移植的人类活体供者中测定了血浆 BA、AVP 和 PVP。
急性胆汁淤积（BDL 或 BA 注射模拟）和门静脉高压（PVS 模拟）均可独立激活 SON 和 AVP 分泌。PH 或 BDL 后 BA 在大脑中积累，并且 TGR5 在 SON 中表达。TGR5 激动剂 OA 模拟 SON 激活，BDL 后 TGR5 KO 小鼠中的 SON 激活被抑制。传入神经途径也有助于 PH 后 AVP 的分泌，因为辣椒素处理或 SCL 导致 PH 后 SON 激活减弱。
在啮齿动物的 PH 后，急性胆汁淤积和门静脉高压通过神经和内分泌途径刺激 AVP 的分泌，这可能保护肝脏免受剪切力和胆汁酸过载的影响。活体供者的数据表明，该途径也可能在人类中起作用。
