异氟烷预处理通过增加大鼠肝脏体内的肝血红素加氧酶活性来降低门静脉阻力。

Isoflurane pretreatment lowers portal venous resistance by increasing hepatic heme oxygenase activity in the rat liver in vivo.

作者信息

Schmidt Rene, Hoetzel Alexander, Baechle Tilo, Loop Torsten, Humar Matjaz, Bauer Michael, Pahl Heike L, Geiger Klaus K, Pannen Benedikt H J

机构信息

Department of Anesthesiology and Critical Care Medicine, University Hospital Freiburg, Hugstetterstrasse 55, D-79106 Freiburg, Germany.

出版信息

J Hepatol. 2004 Nov;41(5):706-13. doi: 10.1016/j.jhep.2004.07.004.

DOI:10.1016/j.jhep.2004.07.004

PMID:15519641

Abstract

BACKGROUND/AIMS: The heme oxygenase (HO) system contributes to the maintenance of hepatic perfusion and integrity. It was the objective of this study to determine the influence of isoflurane (ISO) on hepatic HO-1 induction and its impact on hepatic hemodynamics.

METHODS

Rats were pretreated with or without ISO for 5h. After hemodynamic measurements by pressure-, laser doppler-, and ultrasound based techniques, the liver was harvested. HO-1 was analyzed by an HO activity assay, Northern- and Western blotting.

RESULTS

ISO pretreatment induced hepatic HO-1 mRNA and protein resulting in an increase of HO activity. No effect on hsp-27, hsp-70 and hsp-90 mRNA could be observed. ISO lowered portal resistance. HO inhibition by tin protoporphyrine IX increased portal resistance in ISO pretreated animals up to control levels. This was associated with an increase in portal pressure and a reduction of portal flow. Microvascular flux was also impaired after HO blockade and ISO. However, hepatic arterial and systemic hemodynamics remained unchanged, indicating a specific effect within the portal vascular bed.

CONCLUSIONS

ISO pretreatment induces hepatic HO-1 mRNA and protein followed by an increase in HO activity, thereby reducing portal resistance. These findings indicate a beneficial effect of ISO on hepatic hemodynamics in vivo.

摘要

背景/目的：血红素加氧酶（HO）系统有助于维持肝脏灌注和完整性。本研究的目的是确定异氟烷（ISO）对肝脏HO-1诱导的影响及其对肝脏血流动力学的作用。

方法

对大鼠进行或不进行ISO预处理5小时。通过基于压力、激光多普勒和超声的技术进行血流动力学测量后，摘取肝脏。通过HO活性测定、Northern印迹和Western印迹分析HO-1。

结果

ISO预处理诱导肝脏HO-1 mRNA和蛋白质表达，导致HO活性增加。未观察到对hsp-27、hsp-70和hsp-90 mRNA有影响。ISO降低门静脉阻力。锡原卟啉IX抑制HO可使ISO预处理动物的门静脉阻力增加至对照水平。这与门静脉压力升高和门静脉血流减少有关。HO阻断和ISO处理后微血管通量也受损。然而，肝动脉和全身血流动力学保持不变，表明在门静脉血管床内有特定作用。