Angiotensin II signaling through the AT1a and AT1b receptors does not have a role in the development of cerulein-induced chronic pancreatitis in the mouse.
Angiotensin II signaling through the AT1a and AT1b receptors does not have a role in the development of cerulein-induced chronic pancreatitis in the mouse.
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通过 AT1a 和 AT1b 受体的血管紧张素 II 信号传导在小鼠中雨蛙素诱导的慢性胰腺炎的发展中没有作用。
DOI：
10.1152/ajpgi.00006.2010
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Neuschwander-Tetri,BrentA
中科院分区：
文献类型：
--
作者：
Ulmasov,Barbara;Xu,Zekuan;Talkad,Vanita;Oshima,Kiyoko;Neuschwander-Tetri,BrentA
器官内肾素-血管紧张素系统（RAS）在多种疾病的病理生理学中发挥着重要作用，并且与纤维发生有关。 RAS 在慢性胰腺炎发展中的作用尚未明确。在大鼠模型中，使用血管紧张素转换酶抑制剂 (ACEi) 或血管紧张素受体 1 (AT1) 阻滞剂 (ARB) 阻断 RAS，除少数例外外，大多可减轻胰腺炎症和纤维化。与此同时，人类使用 ACEI 和 ARB 与急性胰腺炎的适度风险相关。本研究的目的是使用 AT1a 和 AT1b 缺陷小鼠以及 ARB 氯沙坦来阐明 AT1 信号通路在胰腺炎发展中的作用。通过在 C57BL/6J 野生型 (WT) 以及 AT1a 和 AT1b 缺陷型小鼠（AT1a−/− 和 AT1b−/−）中重复施用雨蛙素诱导慢性胰腺炎，并在第 10 天评估胰腺损伤。雨蛙素治疗组的胰腺重量显着降低。通过组织学检查评估存在严重的实质萎缩和纤维化。纤维化伴随着胰腺星状细胞（PSC）的激活，通过蛋白质印迹分析评估α-平滑肌肌动蛋白。雨蛙素治疗的 WT、AT1a−/−、AT1b−/− 小鼠或氯沙坦治疗的 WT 小鼠之间在雨蛙素诱导的形态或分子改变方面没有发现差异。我们的结果表明，在重复性雨蛙蛋白损伤诱导的小鼠胰腺炎模型中，AT1a 和 AT1b 受体途径似乎对于胰腺炎的发生并不重要。
The intraorgan renin-angiotensin system (RAS) plays an important role in the pathophysiology of a variety of diseases and has been implicated in fibrogenesis. The role of RAS in the development of chronic pancreatitis is not well established. The blockade of RAS in rat models with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor 1 (AT1) blockers (ARBs) mostly have reduced pancreatic inflammation and fibrosis with a few exceptions. At the same time, the use of ACEi and ARBs in humans is associated with a modest risk of acute pancreatitis. The aim of this study was to elucidate the effect of the AT1 signaling pathway in the development of pancreatitis using AT1a- and AT1b-deficient mice as well as the ARB losartan. Chronic pancreatitis was induced by repetitive cerulein administration in C57BL/6J wild-type (WT) and AT1a- and AT1b-deficient mice (AT1a−/− and AT1b−/−), and pancreatic injury was assessed atday 10. Pancreatic weight of cerulein treated groups was significantly reduced. There was severe parenchymal atrophy and fibrosis assessed by histological examination. Fibrosis was accompanied by activation of pancreatic stellate cells (PSC) evaluated by Western blot analysis for α-smooth muscle actin. No differences were seen between cerulein-treated WT, AT1a−/− , AT1b−/− mice, or losartan treated-WT mice with regards to morphological or molecular alterations induced by cerulein. Our results demonstrate that AT1a and AT1b receptor pathways do not seem to be essential for the development of pancreatitis in the mouse model of pancreatitis induced by repetitive cerulein injury.