肝血窦内皮细胞产生的血管收缩性前列腺素增加，会导致肝硬化大鼠肝脏的门静脉灌注压升高。

Enhanced vasoconstrictor prostanoid production by sinusoidal endothelial cells increases portal perfusion pressure in cirrhotic rat livers.

作者信息

Gracia-Sancho Jorge, Laviña Bàrbara, Rodríguez-Vilarrupla Aina, García-Calderó Héctor, Bosch Jaime, García-Pagán Joan Carles

机构信息

Hepatic Hemodynamic Laboratory, Liver Unit, IMDIM, Hospital Clínic, Ciberehd and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Villarroel 170, 08036 Barcelona, Spain.

出版信息

J Hepatol. 2007 Aug;47(2):220-7. doi: 10.1016/j.jhep.2007.03.014. Epub 2007 Apr 5.

DOI:10.1016/j.jhep.2007.03.014

PMID:17459512

Abstract

BACKGROUND/AIMS: Cyclooxygenase-1 (COX-1) is overexpressed in sinusoidal endothelial cells (SEC) of cirrhotic rat livers, and through an enhanced production of vasoconstrictor prostanoids contributes to increase intrahepatic resistance. Our study was aimed at investigating the role of enhanced AA bioavailability modulating the hepatic vascular tone of cirrhotic livers and identifying which prostanoid is involved.

METHODS

SEC isolated from control and cirrhotic rat livers were incubated with AA, methoxamine or vehicle. TXA(2) was quantified. In addition, portal perfusion pressure (PP) response curves to AA were performed in rat livers pre-incubated with vehicle, SC-560 (COX-1 inhibitor), Furegrelate (inhibitor of TXA(2) synthesis) and SQ-29548 (PGH(2)/TXA(2) receptor blocker). cPLA2 activity was determined in control and cirrhotic livers.

RESULTS

AA and methoxamine incubation promoted a significant increase in TXA(2) release by Cirrhotic-SEC, but not in Control-SEC. AA produced a dose-dependent increase in the PP, associated with increased TXA(2) release. These responses were significantly greater in cirrhotic livers. COX-1 inhibition and PGH(2)/TXA(2) receptor blockade, but not TXA(2) synthase inhibition, markedly attenuated the PP response to AA of cirrhotic livers. Additionally, cirrhotic livers exhibited significantly increased cPLA2 activity.

CONCLUSIONS

An enhanced production of vasoconstrictor prostanoids, probably PGH(2), by SEC contributes to increase vascular tone of cirrhotic livers.

摘要

背景/目的：环氧化酶-1（COX-1）在肝硬化大鼠肝脏的窦状内皮细胞（SEC）中过度表达，并通过增加血管收缩性前列腺素的产生，导致肝内阻力增加。我们的研究旨在探讨增强的花生四烯酸（AA）生物利用度对肝硬化肝脏血管张力的调节作用，并确定涉及哪种前列腺素。

方法

将从对照和肝硬化大鼠肝脏分离的SEC与AA、甲氧明或赋形剂一起孵育。对血栓素A2（TXA2）进行定量。此外，在预先用赋形剂、SC-560（COX-1抑制剂）、呋格雷酯（TXA2合成抑制剂）和SQ-29548（PGH2/TXA2受体阻滞剂）孵育的大鼠肝脏中，进行对AA的门静脉灌注压（PP）反应曲线实验。测定对照和肝硬化肝脏中的胞浆型磷脂酶A2（cPLA2）活性。

结果

AA和甲氧明孵育促进肝硬化SEC释放TXA2显著增加，但对照SEC未增加。AA使PP呈剂量依赖性增加，与TXA2释放增加相关。这些反应在肝硬化肝脏中明显更大。COX-1抑制和PGH2/TXA2受体阻断，但不是TXA2合酶抑制，显著减弱了肝硬化肝脏对AA的PP反应。此外，肝硬化肝脏的cPLA2活性显著增加。