Zipprich Alexander, Loureiro-Silva Mauricio R, Jain Dhanpat, D'Silva Irita, Groszmann Roberto J
Digestive Disease Section, Yale University School of Medicine, New Haven, CT, USA.
J Hepatol. 2008 Nov;49(5):739-45. doi: 10.1016/j.jhep.2008.06.027. Epub 2008 Aug 6.
BACKGROUND/AIMS: Hepatic arterial resistance is modulated by the hepatic arterioles but the role of NO and vascular remodeling in hepatic arterial resistance in cirrhosis is unknown.
Cirrhosis was induced by CCl(4) or BDL. Using a bivascular liver perfusion dose-responses curves to methoxamine were obtained from the hepatic artery in absence and presence of L-NMMA. Lumen-diameter, wall thickness and number of smooth muscle nuclei were quantitated in the arteries using image analysis.
Hepatic arterial resistance and the response to methoxamine were lower in cirrhosis compared to controls (p< or = 0.04) and lower in BDL compared to CCl(4) (p< or = 0.01). L-NMMA increased the response to methoxamine in CCl(4) (p=0.002) and BDL (p=0.05) but corrected the response only in CCl(4) (p=n.s. vs. control). Wall thickness and the number of smooth muscle nuclei were significantly smaller in cirrhosis compared to controls (p<0.05) and the number of nuclei was also lower in BDL compared to CCl(4) (p=0.005).
NO is the main modulator of hepatic arterial resistance in CCl(4) but not in BDL. Intrahepatic arterial remodeling is present in both cirrhotic models but is greater in BDL. This indicates a larger role of structural changes in the control of hepatic arterial resistance in BDL.
背景/目的：肝动脉阻力受肝小动脉调节，但一氧化氮（NO）和血管重塑在肝硬化肝动脉阻力中的作用尚不清楚。
通过四氯化碳（CCl₄）或胆管结扎（BDL）诱导肝硬化。利用双血管肝脏灌注法，在存在和不存在左旋硝基精氨酸甲酯（L-NMMA）的情况下，从肝动脉获得甲氧明的剂量反应曲线。使用图像分析对动脉的管腔直径、壁厚和平滑肌细胞核数量进行定量。
与对照组相比，肝硬化患者的肝动脉阻力和对甲氧明的反应较低（p≤0.04），与CCl₄组相比，BDL组更低（p≤0.01）。L-NMMA增加了CCl₄组（p = 0.002）和BDL组（p = 0.05）对甲氧明的反应，但仅在CCl₄组校正了反应（与对照组相比，p无统计学意义）。与对照组相比，肝硬化患者的壁厚和平滑肌细胞核数量显著更小（p < 0.05），与CCl₄组相比，BDL组的细胞核数量也更低（p = 0.005）。
NO是CCl₄诱导肝硬化中肝动脉阻力的主要调节因子，但在BDL诱导的肝硬化中不是。两种肝硬化模型均存在肝内动脉重塑，但BDL组更明显。这表明结构变化在BDL诱导的肝硬化肝动脉阻力控制中起更大作用。
