Integrative study on hepatic anaphylaxis

作为本研究的第一个项目，我们研究了过敏反应对豚鼠、大鼠和家兔离体灌注致敏肝脏血管阻力分布和肝脏重量的影响。在豚鼠对抗原的反应中，随着肝脏体重的增加，窦前抵抗比窦后抵抗的增加幅度更大，而在大鼠和家兔中观察到几乎选择性的窦前静脉收缩和肝脏体重减轻。其次，用离体卵清蛋白致敏豚鼠肝脏研究了剪切应力在一氧化氮（NO）介导的过敏性静脉收缩衰减中的作用。肝过敏反应可以以剪切应力无关的方式增加NO的产生，并且在窦前和窦后都类似地扩张，而以剪切应力依赖的方式产生的NO主要减弱剪切应力优先增加的窦前静脉收缩。从卵清蛋白致敏豚鼠分离的灌注肝脏中，更多的因素参与了过敏诱导的节段性静脉收缩。我们发现过敏性反应引起的豚鼠肝窦前收缩主要由血小板活化因子和白三烯引起的窦后收缩引起。第四，我们确定了肥大细胞和库普弗细胞（常驻血管内巨噬细胞）在大鼠肝脏过敏反应中的作用。我们发现肝过敏性血管收缩主要是由肥大细胞介导的，但不是唯一的。Kupffer细胞不参与大鼠肝过敏性血管收缩。最后，我们确定了肝脏和内脏血管床在麻醉大鼠过敏性低血压中的作用。我们证明肝脏和内脏血管床可能与过敏性低血压有关，这可能是由于过敏性窦前收缩引起的门静脉高压，导致内脏充血，导致循环血容量减少，从而导致全身动脉低血压。少

As the first project of this research, we studied effects of anaphylaxis on hepatic vascular resistance distribution and liver weight in isolated perfused sensitized livers of guinea pigs, rats, and rabbits. In response to antigen, presinusoidal resistances increased in a greater magnitude than the postsinusoidal resistances with liver weight gain in guinea pigs, while almost selective venoconstriction of the presinusoids and liver weight loss were observed in rats and rabbits. Second, the role of shear stress in nitric oxide (NO)-mediated attenuation of anaphylactic venoconstriction was studied using an isolated ovalbumin-sensitized guinea pig liver. Hepatic anaphylaxis can increase NO production in a shear stress-independent manner, and dilates similarly both pre- and post-sinusoids, while NO produced in a shear stress-dependent manner attenuates predominantly venoconstriction of the presinusoids where shear stress is preferentially increased. Third, we determined what chemical media … More tors are involved in anaphylaxis-induced segmental venoconstriction in perfused livers isolated from ovalbumin sensitized guinea pigs. We found that anaphylaxis-induced pre-sinusoidal constriction is mainly caused by platelet-activating factor and the post-sinusoidal constriction by leukotrienes in guinea pig livers. Fourth, we determined the roles of mast cells and Kupffer cells, resident intravascular macrophages, in rat hepatic anaphylaxis. We showed that hepatic anaphylactic vasoconstriction is mediated mainly by mast cells, but not exclusively. Kupffer cells are not involved in rat hepatic anaphylactic vasoconstriction. Finally, we determined the roles of liver and splanchnic vascular bed in anaphylactic hypotension in anesthetized rats. We demonstrated that liver and splanchnic vascular beds are involved in anaphylactic hypotension presumably due to anaphylactic presinusoidal contraction-induced portal hypertension, which induced splanchnic congestion resulting in a decrease in circulating blood volume and thus systemic arterial hypotension. Less