在晚期大鼠肝纤维化中，1型血管紧张素II受体的表达降低。

Expression of angiotensin II receptor type 1 is reduced in advanced rat liver fibrosis.

作者信息

Töx Ulrich, Scheller Ingo, Kociok Norbert, Kern Michael André, Klanac Dejan, Daudi Sharif Mohammed, Laue Oliver, Schirmacher Peter, Goeser Tobias, Schulte Sigrid, Steffen Hans Michael

机构信息

Department of Gastroenterology, University of Cologne, Cologne, Germany.

出版信息

Dig Dis Sci. 2007 Aug;52(8):1995-2005. doi: 10.1007/s10620-006-9133-1. Epub 2007 Apr 4.

DOI:10.1007/s10620-006-9133-1

PMID:17406843

Abstract

In this study, we assessed the hypothesis that the expression of angiotensin II receptor type 1 (AGTR1) in liver tissue changes with increasing fibrosis, which would influence the antifibrotic efficacy of AGTR1 blockers. Rats were treated with candesartancilexetil (CAN) initiated 8 or 15 days after bile duct occlusion (BDO). Four weeks after BDO, AGTR1 mRNA and protein were decreased compared to those in sham-operated animals depending on the amount of fibrosis. Starting CAN early, but not late, reduced mRNA of profibrotic TGF-beta, MMP2, and Smad2. However, CAN had no significant effect on collagen I, fibrosis, or intrahepatic resistance. In conclusion, progression of liver fibrosis reduces AGTR1 expression. Therefore, in our model, antifibrotic effects of CAN are insufficient to improve fibrosis or intrahepatic resistance. However, if AGTR1 blockade is started early, a decrease in essential profibrotic molecules is achieved. Hence, early initiation of therapy with AGTR1 blockers may be crucial for the prevention of cirrhosis.

摘要

在本研究中，我们评估了以下假说：随着肝纤维化程度加重，肝组织中血管紧张素II 1型受体（AGTR1）的表达会发生变化，这将影响AGTR1阻滞剂的抗纤维化疗效。大鼠在胆管结扎（BDO）后8天或15天开始用坎地沙坦酯（CAN）治疗。BDO四周后，与假手术动物相比，AGTR1 mRNA和蛋白水平随纤维化程度的增加而降低。早期而非晚期开始使用CAN可降低促纤维化因子转化生长因子-β（TGF-β）、基质金属蛋白酶2（MMP2）和Smad2的mRNA水平。然而，CAN对I型胶原蛋白、纤维化或肝内阻力无显著影响。总之，肝纤维化进展会降低AGTR1表达。因此，在我们的模型中，CAN的抗纤维化作用不足以改善纤维化或肝内阻力。然而，如果早期开始AGTR1阻断治疗，则可使重要的促纤维化分子减少。因此，早期开始使用AGTR1阻滞剂治疗对于预防肝硬化可能至关重要。