Steib Christian J, Gerbes Alexander L, Bystron Markus, Op den Winkel Mark, Härtl Josef, Roggel Frigga, Prüfer Thomas, Göke Burkhard, Bilzer Manfred
Department of Medicine II, Klinikum Grosshadern, Ludwig-Maximilians University, Marchioninistrasse 15, 81366 Munich, Germany.
J Hepatol. 2007 Aug;47(2):228-38. doi: 10.1016/j.jhep.2007.03.019. Epub 2007 Apr 9.
BACKGROUND/AIMS: Cirrhotic patients show an increased risk of variceal bleeding upon bacterial infections. Kupffer cells (KC) constitute the first macrophage population to become activated by bacterial beta-glucans and endotoxins derived from the gut. We therefore investigated whether and how KC activation increases portal pressure.
KC in normal and fibrotic livers from bile duct ligated (BDL) rats were activated by the beta-glucan component of zymosan in vivo and during isolated rat liver perfusion.
Activation of KC in normal livers resulted in a severalfold increase of portal pressure in vivo as well as in isolated perfused liver preparations. This increase and the accompanying 40-fold stimulation of hepatic prostaglandin F(2alpha)/D(2) and thromboxane A(2) (TxA(2)) production in isolated perfused livers were attenuated by KC blockade. The TxA(2) synthase inhibitor furegrelate and the TxA(2) receptor antagonist BM 13.177 reduced the increase of portal perfusion pressure supporting TxA(2) as pivotal vasoconstrictor released by activated KC. Importantly, a more pronounced vasopressor response in fibrotic livers was related to a raise in KC density and a 10-fold increase of TxA(2) production after KC activation.
KC activated by beta-glucans increase portal pressure through the release of TxA(2). This vasopressor response is augmented in BDL induced fibrosis.
背景/目的：肝硬化患者在发生细菌感染时静脉曲张出血风险增加。库普弗细胞（KC）是首个被肠道来源的细菌β-葡聚糖和内毒素激活的巨噬细胞群体。因此，我们研究了KC激活是否以及如何增加门静脉压力。
通过酵母聚糖的β-葡聚糖成分在体内及离体大鼠肝脏灌注过程中激活胆管结扎（BDL）大鼠正常肝脏和纤维化肝脏中的KC。
正常肝脏中KC的激活导致体内以及离体灌注肝脏标本中门静脉压力增加数倍。KC阻断可减弱这种增加以及离体灌注肝脏中伴随的肝前列腺素F(2α)/D(2)和血栓素A(2)（TxA(2)）产生的40倍刺激。TxA(2)合酶抑制剂呋格雷酯和TxA(2)受体拮抗剂BM 13.177降低了门静脉灌注压力的增加，支持TxA(2)作为激活的KC释放的关键血管收缩剂。重要的是，纤维化肝脏中更明显的升压反应与KC密度增加以及KC激活后TxA(2)产生增加10倍有关。
β-葡聚糖激活的KC通过释放TxA(2)增加门静脉压力。这种升压反应在BDL诱导的纤维化中增强。
